Lecture 15 Antigen Recognition

Overview


 

In order to initiate an immune response antigen must recognized. be recognized. Antigen recognition depends on detection of antigen by special receptors. receptors. Antigen recognition depends on cellular cooperation. cooperation. Cellular cooperation is controlled by recognition of MHCMHC-encoded receptors.

Clonal Selection Theory

(F. Macfarlane Burnet)


 

prepre-existence of of many different potential antibody producing cells each cell displays surface receptors for specific antigens antigen encounter selects cells What prevents recognition/destruction of self tissues?

Postulates of the Clonal Selection Hypothesis

 

Each lymphocyte bears a single type of receptor of a unique specificity Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphocyte development and are therefore absent from the repertoire

Diversity of Lymphocyte Antigen Receptors

 

  

Variable region of antigen receptor encoded by sets of gene segments During lymphocyte development somatic gene rearrangement create unique combinations of gene segments Once recombinant events have occurred, further rearrangement is prohibited Receptor specificity of a lymphocyte cannot change Each lymphocyte bears many copies of the unique receptor At least 108 different lymphocytes in an individual

Genomic Organization of heavy- and heavylightlight-chain segments

Development of the Antibody Repertoire



The antibody repertoire is generated during B cell development by DNA rearrangements that combine and assemble variable-region gene variablesegments (somatic diversification theory) (somatic theory) Diversity is enhanced by hypermutation in mature B cells (germline theory) (germline theory)

Some Comments on Cluster of Differentiation/Designation (CD) Antigens



What are they?

 

Differentiation antigens Expressed by cells at distinct stages of differentiation Expressed by cells having different functions

How are they detected?

FluorescenceFluorescence-Activated Cell Sorting (FACS)

Lymphocyte Populations
  

B lymphocytes Plasma cells T lymphocytes

 

Helper/Inducer (CD4) Suppressor (CD8)

T Cell Recognition of Antigen



  

Recognize antigen peptide fragments bound to specialize cell surface molecules on antigen-presenting cells (APC). antigenMolecules are encoded by major histocompatibility complex Peptides are displayed to T cells as peptide:MHC complexes T cell antigen receptors recognize peptide:MHC complexes Each MHC molecule can bind numerous different peptides Two classes of MHC molecules

Major Histocompatibility Complex (MHC) Gene Products



Class I


Antigen is usually endogenous (e.g. viral proteins). CD8+ Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with class I MHC gene product on APC. Antigen is usually extracellular. extracellular. CD4+ Helper T Lymphocytes recognize antigen in association with class II MHC gene product on APC.

Class II Molecules
 

Cellular Cooperation and Antigen Recognition

+

APC

Extracellular Antigen

Class II MHC- CD4+ Helper T MHCassociated Lymphocyte antigen

B Cell Antigen Recognition



Cell surface immunoglobulin receptor or B-cell receptor B(IgM and IgD) Antigen contact initiates B-cell activation, clonal Bexpansion, maturation to plasma cell Antigen receptor is identical to immunoglobulin that will ultimately be produced

Cellular Cooperation
antigen TH B

Plasma Cells Antigen presentation to T and B cells by APC T cells elaborate cytokines to facilitate B cell proliferation and maturation Antibody secretion by plasma cells

Antigen presenting cell

Clonal Expansion Following Antigen Exposure

Virgin lymphocyte pool

PRIMARY RESPONSE

effector cells

memory cell pool SECONDARY RESPONSE

effector cells

memory cell pool

The Bottom Line

 

In order to initiate an immune response recognized. antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. receptors. Antigen recognition depends on cellular cooperation. cooperation. Cellular cooperation is controlled by MHCrecognition of MHC-encoded receptors. Antigen drives the process resulting in effector cells and memory cells.