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Major histocompatibility complex

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MHC-I molecule

The major histocompatibility complex (MHC) is a set of cell surface proteins essential for
acquired immune system to recognize foreign molecules in vertebrates, which in turn
determines histocompatibility. The main function of MHC molecules is to bind to peptide
fragments derived from pathogens and display them on the cell surface for recognition by
the appropriate T-cells.[1] MHC molecules mediate interactions of leukocytes, also called
white blood cells (WBCs), which are immune cells, with other leukocytes or with body cells.
The MHC determines compatibility of donors for organ transplant, as well as one's
susceptibility to an autoimmune disease via crossreacting immunization. In humans, the
MHC is also called the human leukocyte antigen (HLA).

In a cell, protein molecules of the host's own phenotype or of other biologic entities are
continually synthesized and degraded. Each MHC molecule on the cell surface displays a
molecular fraction of a protein, called an epitope.[2] The presented antigen can be either
'self' or 'nonself', thus preventing an organism`s immune system targeting its own cells. In
its entirety, the MHC population is like a meter indicating the balance of proteins within the
cell.

The MHC gene family is divided into three subgroups: class I, class II, and class III. Class I
MHC molecules have β2 subunits so can only be recognised by CD8 co-receptors. Class II
MHC molecules have no β2 subunits so can be recognised by CD4 co-receptors. In this
way MHC molecules chaperones which type of lymphocytes may bind to the given antigen
with high affinity, since different lymphocytes express different TCR co-receptors.

Diversity of antigen presentation, mediated by MHC classes I and II, is attained in at least
three ways: (1) an organism's MHC repertoire is polygenic (via multiple, interacting genes);
(2) MHC expression is codominant (from both sets of inherited alleles); (3) MHC gene
variants are highly polymorphic (diversely varying from organism to organism within a
species).[3] Major histocompatibility complex and sexual selection has been observed in
male mice making mate choices of females with different MHCs and thus demonstrating
sexual selection. Also, at least for MHC I presentation, there has been evidence of antigenic
peptide splicing which can combine peptides from different proteins, vastly increasing
antigen diversity.

Discovery
The first descriptions of the MHC were made by British immunologist Peter Gorer in 1936.
[4] MHC genes were first identified in inbred mice strains. Clarence Little transplanted
tumors across differing strains and found rejection of transplanted tumors according to
strains of host versus donor.[5] George Snell selectively bred two mouse strains, attained a
new strain nearly identical to one of the progenitor strains, but differing crucially in
histocompatibility—that is, tissue compatibility upon transplantation—and thereupon
identified an MHC locus.[6] For this work, Snell was awarded the 1980 Nobel Prize in
Physiology or Medicine, together with Baruj Benacerraf and Jean Dausset.

In immunity
Of the three MHC classes identified, attention commonly focuses on classes I and II. By
interacting with CD4 molecules on surfaces of helper T cells, MHC class II mediates
establishment of specific immunity (also called acquired immunity or adaptive immunity).
By interacting with CD8 molecules on surfaces of cytotoxic T cells, MHC class I mediates
destruction of infected or malignant host cells, the aspect of specific immunity termed
cellular immunity. (The other arm of specific immunity is humoral immunity, whose relation
to MHC is more indirect.)

Functions

MHC is the tissue-antigen that allows the immune system (more specifically T cells) to bind
to, recognize, and tolerate itself (autorecognition). MHC is also the chaperone for
intracellular peptides that are complexed with MHCs and presented to TCRs as potential
foreign antigens. MHC interacts with TCR and its co-receptors to optimize binding
conditions for the TCR-antigen interaction, in terms of antigen binding affinity and
specificity, and signal transduction effectiveness.

Essentially, the MHC-peptide complex is a complex of autoantigen/alloantigen. Upon

binding, T cells should in principle tolerate the auto-antigen, while activate when exposed to
the allo-antigen. Disease states occur when this principle is disrupted.

Antigen presentation: MHC molecules bind to both T cell receptor and CD4/CD8 co-
receptors on T lymphocytes, and the antigen epitope held in the peptide-binding groove of
the MHC molecule interacts with the variable Ig-Like domain of the TCR to trigger T-cell
activation [7]

Autoimmune reaction: Having some MHC molecules increases the risk of autoimmune
diseases more than having others. HLA-B27 is an example. It is unclear how exactly having
the HLA-B27 tissue type increases the risk of ankylosing spondylitis and other associated
inflammatory diseases, but mechanisms involving aberrant antigen presentation or T cell
activation have been hypothesized.

Tissue allorecognition: MHC molecules in complex with peptide epitopes are essentially
ligands for TCR. T cells become activated by binding to the peptide-binding grooves of any
MHC molecule that T cells were not entrained to recognize during thymus positive
selection.
Lymphocytes

As a lineage of leukocytes, lymphocytes reside in peripheral lymphoid tissues, including

lymphoid follicles and lymph nodes, and include B cells, T cells, and natural killer cells (NK
cells). B cells, which act specifically, secrete antibody molecules, but do not bind MHC. T
cells, which act specifically, as well as NK cells, which act innately, interact with MHC. NK
cells express Killer Ig-like receptors (KIRs) that bind to MHC I molecules and signal through
ITIM (immunoreceptor tyrosine inhibition motif) recruitment and activation of protein
tyrosine phosphatases. This means in contrast to CD8/TCR interaction that activates Tc
lymphocytes, NK cells becomes deactivated when bound to MHC I. When MHC class I
expression is low, as is typically the case with abnormal cell function during viral infection
or tumourigenesis, NK cells lose the inhibitory KIR signal and trigger programmed cell
death of the abnormal cell. NK cells thus help prevent progress of cancerous cells by
contributing to tumor surveillance.

MHC class II

MHC class II can be conditionally expressed by all cell types, but normally occurs only on
professional antigen-presenting cells (APCs): macrophages, B cells, and especially
dendritic cells (DCs). An APC takes up an antigen, performs antigen processing, and
returns a molecular fraction of it—a fraction termed the epitope—to the APC's surface,
coupled within an MHC class II molecule mediating antigen presentation by displaying this
epitope. On the cell's surface, the epitope can contact its cognate region on immunologic
structures recognizing that epitope. That molecular region which binds to—or, in jargon,
ligates—the epitope is the paratope.

On surfaces of helper T cells are CD4 receptors, as well as T cell receptors (TCRs). When a
naive helper T cell's CD4 molecule docks to an APC's MHC class II molecule, its TCR can
meet and be imprinted by the epitope coupled within the MHC class II. This event primes
the naive helper T cell. According to the local milieu, that is, the balance of cytokines
secreted by APCs in the microenvironment, the naive helper T cell (Th0) polarizes into either
a memory Th cell or an effector Th cell of phenotype either type 1 (Th1), type 2 (Th2), type
17 (Th17), or regulatory/suppressor (Treg), as so far identified, the Th cell's terminal
differentiation.

MHC class II thus mediates immunization to—or, if APCs polarize Th0 cells principally to
Treg cells, immune tolerance of—an antigen. The polarization during primary exposure to an
antigen is key in determining a number chronic diseases, such as inflammatory bowel
diseases and asthma, by skewing the immune response that memory Th cells coordinate
when their memory recall is triggered upon secondary exposure to similar antigens. (B
cells express MHC class II to present antigen to Th0, but when their B cell receptors bind
matching epitopes, interactions which are not mediated by MHC, these activated B cells
secrete soluble immunoglobulins: antibody molecules mediating humoral immunity.)

MHC class I

MHC class I occurs on all nucleated cells—in essence all cells but red blood cells—and
presents epitopes to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL
expresses CD8 receptors, in addition to TCRs. When a CTL's CD8 receptor docks to a MHC
class I molecule, if the CTL's TCR fits the epitope within the MHC class I molecule, the CTL
triggers the cell to undergo programmed cell death by apoptosis. Thus, MHC class I helps
mediate cellular immunity, a primary means to address intracellular pathogens, such as
viruses and some bacteria, including bacterial L forms, bacterial genus Mycoplasma, and
bacterial genus Rickettsia.

Genes
MHC gene families are found in all vertebrates, though they vary widely. In humans, the
MHC region occurs on chromosome 6, between the flanking genetic markers MOG and
COL11A2 (from 6p22.1 to 6p21.3 about 29Mb to 33Mb on the hg19 assembly), and
contains 240 genes spanning 3.6 megabase pairs (3 600 000 bases).[8] About half have
known immune functions.

The same markers in the gray short-tailed opossum (Monodelphis domestica), a marsupial,
span 3.95 Mb, yielding 114 genes, 87 shared with humans.[9] Marsupial MHC genotypic
variation lies between eutherian mammals and birds, taken as minimal MHC encoding, but
is closer in organization to that of nonmammals, and MHC class I genes of marsupials
have amplified within the class II region, yielding a unique class I/II region.[9]
Class III functions very differently from class I and class II, but its locus occurs between
the other two classes, on chromosome 6 in humans, and are frequently discussed
together.

Class Encoding Expression

One chain, called α, whose

(1) peptide-binding proteins, which select short
ligands are the CD8 receptor
sequences of amino acids for antigen presentation,
I —borne notably by cytotoxic
as well as (2) molecules aiding antigen-processing
T cells—and inhibitory
(such as TAP and tapasin).
receptors borne by NK cells

(1) peptide-binding proteins and (2) proteins Two chains, called α & β,
assisting antigen loading onto MHC class II's whose ligands are the CD4
II
peptide-binding proteins (such as MHC II DM, MHC receptors borne by helper T
II DQ, MHC II DR, and MHC II DP). cells.

Other immune proteins, outside antigen processing

and presentation, such as components of the
III complement cascade (e.g., C2, C4, factor B), the Various
cytokines of immune signaling (e.g., TNF-α), and
heat shock proteins buffering cells from stresses

Proteins
MHC proteins have immunoglobulin-like structure.

MHC class I protein molecule

Class I
Main article: MHC class I

MHC I occurs as an α chain composed of three domains—α1, α2, and α3. The α1 rests upon
a unit of the non-MHC molecule β2 microglobulin (encoded on human chromosome 15).
The α3 domain is transmembrane, anchoring the MHC class I molecule to the cell
membrane. The peptide being presented is held by the floor of the peptide-binding groove,
in the central region of the α1/α2 heterodimer (a molecule composed of two nonidentical
subunits). The genetically encoded and expressed sequence of amino acids, the sequence
of residues, of the peptide-binding groove's floor determines which particular peptide
residues it binds.[10]

MHC class II protein molecule

Classical MHC molecules present epitopes to the TCRs of CD8+ T lymphocytes.

Nonclassical molecules (MHC class IB) exhibit limited polymorphism, expression patterns,
and presented antigens; this group is subdivided into a group encoded within MHC loci
(e.g., HLA-E, -F, -G), as well as those not (e.g., stress ligands such as ULBPs, Rae1, and
H60); the antigen/ligand for many of these molecules remain unknown, but they can
interact with each of CD8+ T cells, NKT cells, and NK cells.

Class II
Main article: MHC class II

MHC class II is formed of two chains, α and β, each having two domains—α1 and α2 and β1
and β2—each chain having a transmembrane domain, α2 and β2, respectively, anchoring
the MHC class II molecule to the cell membrane.[11] The peptide-binding groove is formed
of the heterodimer of α1 and β1.

MHC class II molecules in humans have five to six isotypes. Classic molecules present
peptides to CD4+ lymphocytes. Nonclassic molecules, accessories, with intracellular
functions, are not exposed on cell membranes, but in internal membranes in lysosomes,
normally loading the antigenic peptides onto classic MHC class II molecules.

Class III

Class III molecules have physiologic roles unlike classes I and II, but are encoded between
them in the short arm of human chromosome 6. Class III molecules include several
secreted proteins with immune functions: components of the complement system (such as
C2, C4, and B factor), cytokines (such as TNF-α, LTA, and LTB), and heat shock proteins.

Antigen processing and presentation

MHC class I pathway: Proteins in the cytosol are degraded by the proteasome, liberating peptides internalized by
TAP channel in the endoplasmic reticulum, there associating with MHC-I molecules freshly synthesized. MHC-
I/peptide complexes enter Golgi apparatus, are glycosylated, enter secretory vesicles, fuse with the cell
membrane, and externalize on the cell membrane interacting with T lymphocytes.
Peptides are processed and presented by two classical pathways:

In MHC class II, phagocytes such as macrophages and immature dendritic cells take up
entities by phagocytosis into phagosomes—though B cells exhibit the more general
endocytosis into endosomes—which fuse with lysosomes whose acidic enzymes cleave
the uptaken protein into many different peptides. Via physicochemical dynamics in
molecular interaction with the particular MHC class II variants borne by the host, encoded
in the host's genome, a particular peptide exhibits immunodominance and loads onto MHC
class II molecules. These are trafficked to and externalized on the cell surface.[12]

In MHC class I, any nucleated cell normally presents cytosolic peptides, mostly self
peptides derived from protein turnover and defective ribosomal products. During viral
infection, intracellular microorganism infection, or cancerous transformation, such
proteins degraded in the proteosome are as well loaded onto MHC class I molecules and
displayed on the cell surface. T lymphocytes can detect a peptide displayed at 0.1%-1% of
the MHC molecules.
Peptide binding for Class I and Class II MHC molecules, showing the binding of peptides between the alpha-
helix walls, upon a beta-sheet base. The difference in binding positions is shown. Class I primarily makes
contact with backbone residues at the Carboxy and amino terminal regions, while Class II primarily makes
contacts along the length of the residue backbone. The precise location of binding residues is determined by the
 MHC allele.[13]

Table 2. Characteristics of the antigen processing pathways

Characteristic MHC-I pathway MHC-II pathway

Composition of the Polymorphic chain α and β2

Polymorphic chains α and β,
stable peptide-MHC microglobulin, peptide bound to
peptide binds to both
complex α chain

Dendritic cells, mononuclear

Types of antigen phagocytes, B lymphocytes,
All nucleated cells
presenting cells (APC) some endothelial cells,
epithelium of thymus

T lymphocytes able to Cytotoxic T lymphocytes Helper T lymphocytes

respond (CD8+) (CD4+)

cytosolic proteins (mostly Proteins present in

Origin of antigenic synthetized by the cell; may endosomes or lysosomes
proteins also enter from the extracellular (mostly internalized from
medium via phagosomes) extracellular medium)

Proteases from endosomes

Enzymes responsible for
Cytosolic proteasome and lysosomes (for instance,
peptide generation
cathepsin)

Location of loading the

Specialized vesicular
peptide on the MHC Endoplasmic reticulum
compartment
molecule

Molecules implicated in
 transporting the peptides TAP (transporter associated DM, invariant chain
and loading them on the with antigen processing)
MHC molecules

T lymphocyte recognition restrictions

Main article: MHC restriction

In their development in the thymus, T lymphocytes are selected to recognize MHC

molecules of the host, but not recognize other self antigens. Following selection, each T
lymphocyte shows dual specificity: The TCR recognizes self MHC, but only non-self
antigens.

MHC restriction occurs during lymphocyte development in the thymus through a process
known as positive selection. T cells that do not receive a positive survival signal —
mediated mainly by thymic epithelial cells presenting self peptides bound to MHC
molecules — to their TCR undergo apoptosis. Positive selection ensures that mature T cells
can functionally recognize MHC molecules in the periphery (i.e. elsewhere in the body).

The TCRs of T lymphocytes recognise only sequential epitopes, also called linear epitopes,
of only peptides and only if coupled within an MHC molecule. (Antibody molecules
secreted by activated B cells, though, ligate diverse epitopes—peptide, lipid, carbohydrate,
and nucleic acid—and recognize conformational epitopes, which have three-dimensional
structure.)

In sexual mate selection

Main article: Major histocompatibility complex and sexual selection See also: Interpersonal compatibility
Black-Throated Blue Warbler

MHC molecules enable immune system surveillance of the population of protein molecules
in a host cell, and greater MHC diversity permits greater diversity of antigen presentation.
In 1976, Yamazaki et al demonstrated a sexual selection mate choice by male mice for
females of a different MHC. Similar results have been obtained with fish[14] and birds (e.g.,
black-throated blue warblers).[15] Some data find lower rates of early pregnancy loss in
human couples of dissimilar MHC genes.[16]

MHC may be related to mate choice in some human populations, a theory that found
support by studies by Ober and colleagues in 1997,[17] as well as by Chaix and colleagues
in 2008.[18] However, the latter findings have been controversial.[19] If it exists, the
phenomenon might be mediated by olfaction, as MHC phenotype appears strongly involved
in the strength and pleasantness of perceived odour of compounds from sweat. Fatty acid
esters—such as methyl undecanoate, methyl decanoate, methyl nonanoate, methyl
octanoate, and methyl hexanoate—show strong connection to MHC.[20]

In 1995, Claus Wedekind found that in a group of female college students who smelled T-
shirts worn by male students for two nights (without deodorant, cologne, or scented
soaps), by far most women chose shirts worn by men of dissimilar MHCs, a preference
reversed if the women were on oral contraceptives.[21] Results of a 2002 experiment
likewise suggest HLA-associated odors influence odor preference and may mediate social
cues.[22] In 2005 in a group of 58 subjects, women were more indecisive when presented
with MHCs like their own,[23] although with oral contraceptives, the women showed no
particular preference.[24] No studies show the extent to which odor preference determines
mate selection (or vice versa).

Evolutionary diversity
Most mammals have MHC variants similar to those of humans, who bear great allelic
diversity, especially among the nine classical genes—seemingly due largely to gene
duplication—though human MHC regions have many pseudogenes. The most diverse loci,
namely HLA-A, HLA-B, and HLA-DRB1, have roughly 1000, 1600, and 870 known alleles,
respectively[citation needed].[25] Many HLA alleles are ancient, sometimes of greater homology
to a chimpanzee MHC alleles than to some other human alleles of the same gene.

MHC allelic diversity has challenged evolutionary biologists for explanation. Most posit
balancing selection (see polymorphism (biology)), which is any natural selection process
whereby no single allele is absolutely most fit, such as frequency-dependent selection and
heterozygote advantage. Recent models suggest a high number of alleles is implausible
via heterozygote advantage alone.[citation needed]

Pathogenic coevolution, a counterhypothesis, posits that common alleles are under

greatest pathogenic pressure, driving positive selection of uncommon alleles—moving
targets, so to say, for pathogens. As pathogenic pressure on the previously common alleles
decreases, their frequency in the population stabilizes, and remain circulating in a large
population. Despite great MHC polymorphism at the population level, an individual bears at
most 18 MHC I or II alleles.

Relatively low MHC diversity has been observed in the cheetah (Acinonyx jubatus),[26]
Eurasian beaver (Castor fiber),[27] and giant panda (Ailuropoda melanoleuca).[28] In 2007 low
MHC diversity was attributed a role in disease susceptibility in the Tasmanian devil
(Sarcophilus harrisii), native to the isolated island of Tasmania, such that an antigen of a
transmissible tumor, involved in devil facial tumour disease, appears to be recognized as a
self antigen.[29] To offset inbreeding, efforts to sustain genetic diversity in populations of
endangered species and of captive animals have been suggested.

In transplant rejection
In a transplant procedure, as of an organ or stem cells, MHC molecules act themselves as
antigens and can provoke immune response in the recipient, thus causing transplant
rejection. MHC molecules were identified and named after their role in transplant rejection
between mice of different strains, though it took over 20 years to clarify MHC's role in
presenting peptide antigens to cytotoxic T lymphocytes (CTLs).[30]

Each human cell expresses six MHC class I alleles (one HLA-A, -B, and -C allele from each
parent) and six to eight MHC class II alleles (one HLA-DP and -DQ, and one or two HLA-DR
from each parent, and combinations of these). The MHC variation in the human population
is high, at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR, and
90 alleles for DQ. Any two individuals who are not identical twins will express differing
MHC molecules. All MHC molecules can mediate transplant rejection, but HLA-C and HLA-
DP, showing low polymorphism, seem least important. [clarification needed]

When maturing in the thymus, T lymphocytes are selected for their TCR incapacity to
recognize self antigens, yet T lymphocytes can react against the donor MHC's peptide-
binding groove, the variable region of MHC holding the presented antigen's epitope for
recognition by TCR, the matching paratope. T lymphocytes of the recipient take the
incompatible peptide-binding groove as nonself antigen. The T lymphocytes' recognition of
the foreign MHC as self is allorecognition. [clarification needed]

Transplant rejection has various types known to be mediated by MHC (HLA):

Hyperacute rejection occurs when, before the transplantation, the recipient has preformed
anti-HLA antibodies, perhaps by previous blood transfusions (donor tissue that includes
lymphocytes expressing HLA molecules), by anti-HLA generated during pregnancy
(directed at the father's HLA displayed by the fetus), or by previous transplantation;

Acute cellular rejection occurs when the recipient's T lymphocytes are activated by the
donor tissue, causing damage via mechanisms such as direct cytotoxicity from CD8 cells.

Acute humoral rejection and chronic disfunction occurs when the recipient's anti-HLA
antibodies form directed at HLA molecules present on endothelial cells of the transplanted
tissue.

In all of the above situations, immunity is directed at the transplanted organ, sustaining
lesions. A cross-reaction test between potential donor cells and recipient serum seeks to
detect presence of preformed anti-HLA antibodies in the potential recipient that recognize
donor HLA molecules, so as to prevent hyperacute rejection. In normal circumstances,
compatibility between HLA-A, -B, and -DR molecules is assessed. The higher the number of
incompatibilities, the lower the five-year survival rate. Global databases of donor
information enhance the search for compatible donors.

HLA biology

Codominant expression of HLA genes Main article: Human leukocyte antigen

Human MHC class I and II are also called human leukocyte antigen (HLA). To clarify the
usage, some of the biomedical literature uses HLA to refer specifically to the HLA protein
molecules and reserves MHC for the region of the genome that encodes for this molecule,
but this is not a consistent convention.

The most studied HLA genes are the nine classical MHC genes: HLA-A, HLA-B, HLA-C, HLA-
DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1. In humans, the MHC gene
cluster is divided into three regions: classes I, II, and III. The A, B and C genes belong to
MHC class I, whereas the six D genes belong to class II.

MHC alleles are expressed in codominant fashion.[11] This means the alleles (variants)
inherited from both parents are expressed equally:

Each person carries 2 alleles of each of the 3 class-I genes, (HLA-A, HLA-B and HLA-C), and
so can express six different types of MHC-I (see figure).
In the class-II locus, each person inherits a pair of HLA-DP genes (DPA1 and DPB1, which
encode α and β chains), a couple of genes HLA-DQ (DQA1 and DQB1, for α and β chains),
one gene HLA-DRα (DRA1), and one or more genes HLA-DRβ (DRB1 and DRB3, -4 or -5). That
means that one heterozygous individual can inherit six or eight functioning class-II alleles,
three or more from each parent. The role of DQA2 or DQB2 is not verified. The DRB2, DRB6,
DRB7, DRB8 and DRB9 are pseudogenes.

The set of alleles that is present in each chromosome is called the MHC haplotype. In
humans, each HLA allele is named with a number. For instance, for a given individual, his
haplotype might be HLA-A2, HLA-B5, HLA-DR3, etc... Each heterozygous individual will
have two MHC haplotypes, one each from the paternal and maternal chromosomes.

The MHC genes are highly polymorphic; many different alleles exist in the different
individuals inside a population. The polymorphism is so high, in a mixed population
(nonendogamic), no two individuals have exactly the same set of MHC molecules, with the
exception of identical twins.

The polymorphic regions in each allele are located in the region for peptide contact. Of all
the peptides that could be displayed by MHC, only a subset will bind strongly enough to any
given HLA allele, so by carrying two alleles for each gene, a much larger set of peptides can
be presented.

On the other hand, inside a population, the presence of many different alleles ensures there
will always be an individual with a specific MHC molecule able to load the correct peptide
to recognize a specific microbe. The evolution of the MHC polymorphism ensures that a
population will not succumb to a new pathogen or a mutated one, because at least some
individuals will be able to develop an adequate immune response to win over the pathogen.
The variations in the MHC molecules (responsible for the polymorphism) are the result of
the inheritance of different MHC molecules, and they are not induced by recombination, as
it is the case for the antigen receptors.

Because of the high levels of allelic diversity found within its genes, MHC has also
attracted the attention of many evolutionary biologists.[citation needed]

See also
Cell-mediated immunity Disassortative sexual selection Humoral immunity MHC multimer
Transplant rejection

Notes and references

^ Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in
Health and Disease. 5th edition. New York: Garland Science; 2001 The Major
Histocompatibility Complex and Its Functions

^ Kimball's Biology Histocompatibility Molecules

^ Janeway CA Jr, Travers P, Walport M, et al, Immunobiology: The Immune System in Health
and Disease, 5th edn (New York: Garland Science, 2001), "The major histocompatibility
complex and its functions" .

^ Klein J 1986, "Seeds of time: Fifty years ago Peter A. Gorer discovered the H-2
complex",Immunogenetics 24:331-338

^ Little CC 1941, "The genetics of tumor transplantation", pp 279–309, in Biology of the

Laboratory Mouse, ed by Snell GD, New York: Dover.

^ Snell GD & Higgins GF 1951, "Alleles at the histocompatibility-2 locus in the mouse as
determined by tumor transplantation", Genetics 36:306–310

^ Thomas J. Kindt; Richard A. Goldsby; Barbara Anne Osborne; Janis Kuby (2007). Kuby
immunology . Macmillan. ISBN 978-1-4292-0211-4. Retrieved 28 November 2010.

^ MHC Sequencing Consortium (1999). "Complete sequence and gene map of a human
major histocompatibility complex". Nature 401 (6756): 921–923. doi:10.1038/44853 .
PMID 10553908 .

^ a b Belov K, Deakin JE, Papenfuss AT, Baker ML, Melman SD, Siddle HV, Gouin N, Goode
DL, Sargeant TJ, Robinson MD, Wakefield MJ, Mahony S, Cross JG, Benos PV, Samollow
PB, Speed TP, Graves JA, Miller RD (March 2006). "Reconstructing an ancestral
mammalian immune supercomplex from a marsupial major histocompatibility complex" .
PLoS Biol. 4 (3): e46. doi:10.1371/journal.pbio.0040046 . PMC 1351924 .
PMID 16435885 .
^ Toh H, Savoie CJ, Kamikawaji N, Muta S, Sasazuki T, Kuhara S (October 2000). "Changes
at the floor of the peptide-binding groove induce a strong preference for proline at position
3 of the bound peptide: molecular dynamics simulations of HLA-A*0217". Biopolymers 54
(5): 318–27. doi:10.1002/1097-0282(20001015)54:5<318::AID-BIP30>3.0.CO;2-T .
PMID 10935972 .

^ a b Abbas; Lichtman A.H. (2009). "Ch.3 Antigen capture and presentation to lymphocytes".
Basic Immunology. Functions and disorders of the immune system (3rd ed.). p. A.B. ISBN 978-
1-4160-4688-2.

^ Aderem A, Underhill DM (1999). "Mechanisms of phagocytosis in macrophages". Annu.

Rev. Immunol. 17: 593–623. doi:10.1146/annurev.immunol.17.1.593 . PMID 10358769 .

^ K. Murphy, “Antigen recognition by T cells,” in Janeway's Immunobiology, 8th, Ed., Garland

Science, 2012, pp. 138-153.

^ Boehm T; Zufall F (2006). "MHC peptides and the sensory evaluation of genotype". Trends
Neurosci 29 (2): 100–107. doi:10.1016/j.tins.2005.11.006 . PMID 16337283 .

^ Smith, S.B.; Webster, M.S.; Holmes, R.T. (2005). "The heterozygosity theory of extra-pair
mate choice in birds: a test and a cautionary note" . Journal of Avian Biology 36: 146–154.
doi:10.1111/j.0908-8857.2005.03417.x .(subscription required)

^ Haig D (November 1997). "Maternal-fetal interactions and MHC polymorphism". J. Reprod.

Immunol. 35 (2): 101–9. doi:10.1016/s0165-0378(97)00056-9 . PMID 9421795 .

^ Ober C, Weitkamp LR, Cox N, Dytch H, Kostyu D, Elias S (September 1997). "HLA and mate
choice in humans." . Am. J. Hum. Genet. 61 (3): 497–504. doi:10.1086/515511 .
PMC 1715964 . PMID 9326314 .

^ Chaix R, Chen C, Donnelly P (September 2008). "Is Mate Choice in Humans MHC-
Dependent?" . PLoS Genetics 4 (9): e1000184. doi:10.1371/journal.pgen.1000184 .
PMC 2519788 . PMID 18787687 .

^ Derti A, Cenik C, Kraft P, Roth FP (April 2010). "Absence of evidence for MHC-dependent
mate selection within HapMap populations" . PLoS Genetics 6 (4): e1000925.
doi:10.1371/journal.pgen.1000925 . PMC 2861700 . PMID 20442868 .

^ Janeš D, Klun I, Vidan-Jeras B, Jeras M, Kreft S (2010). "Influence of MHC on odour

perception of 43 chemicals and body odor". Central European Journal of Biology 5 (3): 324–
330. doi:10.2478/s11535-010-0020-6 .
^ Wedekind C, Seebeck T, Bettens F, Paepke AJ (June 1995). "MHC-dependent mate
preferences in humans". Proc. Biol. Sci. 260 (1359): 245–9. doi:10.1098/rspb.1995.0087 .
PMID 7630893 .

^ Jacob S, McClintock MK, Zelano B, Ober C (February 2002). "Paternally inherited HLA
alleles are associated with women's choice of male odor". Nat. Genet. 30 (2): 175–9.
doi:10.1038/ng830 . PMID 11799397 .

^ Santos, P S; Schinemann JA; Gabardo J; Bicalho MG (April 2005). "New evidence that the
MHC influences odor perception in humans: A study with 58 southern Brazilian students".
Horm Behav. 47 (4): 384–388. doi:10.1016/j.yhbeh.2004.11.005 . PMID 15777804 .

^ "The pill makes women pick bad mates" ^ HLA Alleles Numbers

^ Castro-Prieto A, Wachter B, Sommer S (April 2011). "Cheetah paradigm revisited: MHC

diversity in the world's largest free-ranging population". Mol. Biol. Evol. 28 (4): 1455–68.
doi:10.1093/molbev/msq330 . PMID 21183613 .

^ Babik W, Durka W, Radwan J (December 2005). "Sequence diversity of the MHC DRB gene
in the Eurasian beaver (Castor fiber)". Mol. Ecol. 14 (14): 4249–57. doi:10.1111/j.1365-
294X.2005.02751.x . PMID 16313590 .

^ Zhu L, Ruan XD, Ge YF, Wan QH, Fang SG (2007). "Low major histocompatibility complex
class II DQA diversity in the Giant Panda (Ailuropoda melanoleuca)" . BMC Genet. 8: 29.
doi:10.1186/1471-2156-8-29 . PMC 1904234 . PMID 17555583 .

^ Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ, Pyecroft S, Woods GM, Belov K
(October 2007). "Transmission of a fatal clonal tumor by biting occurs due to depleted
MHC diversity in a threatened carnivorous marsupial" . Proc. Natl. Acad. Sci. U.S.A. 104
(41): 16221–6. doi:10.1073/pnas.0704580104 . PMC 1999395 . PMID 17911263 .

^ Abbas; Lichtman A.H. (2009). "Ch.10 Immune responses against tumors and transplant".
Basic Immunology. Functions and disorders of the immune system (3rd ed.). p. A.B. ISBN 978-
1-4160-4688-2.

Bibliography
Daniel M. Davis, The Compatibility Gene, London, Penguin Books, 2014 (ISBN 978-0-241-
95675-5).

External links
Major Histocompatibility Complex at the US National Library of Medicine Medical Subject
Headings (MeSH)

Molecular individuality (German online-book 2012)

Sexual attraction is linked to MHC compatibility

NetMHC 3.0 server — predicts binding of peptides to a number of different MHC (HLA)
alleles

T-cell Group - Cardiff University The story of 2YF6: A Chicken MHC

RCSB Protein Data Bank: Molecule of the Month - Major Histocompatibility Complex

dbMHC Home, NCBI's database of the Major Histocompatibility Complex

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