CHAPTER

Antigen Presentation

SUMMARY
T cells recognize peptide fragments that have
been processed and become bound to major
histocompatibility complex (MHC) class I or II
molecules. These MHCantigen complexes are
presented at the cell surface.
MHC class I molecules associate with endogenously
synthesized peptides, binding to peptides produced
by degradation of the cells internal molecules.
This type of antigen processing is carried out by
proteasomes (which cleave the proteins) and transporters
(which take the fragments to the endoplasmic
reticulum [ER]).
MHC class II molecules bind to peptides produced
following the breakdown of proteins that the cell has
endocytosed. The peptides produced by degradation of
these external antigens are loaded onto MHC class II
molecules in a specialized endosomal compartment
called MIIC.
Cross-presentation allows APCs to acquire antigens from
infected cells. A specialized pathway allows the acquisition
of antigens from infected cells by APCs. This pathway,
called cross-presentation, allows the display of exogenous
antigens by MHC class I molecules.

T CELLS RECOGNIZE PEPTIDE

FRAGMENTS BOUND TO MHC
MOLECULES

Antigens recognized by T cells are degraded or processed

in some way so that the determinant recognized by the
T cell receptor (TCR) is only a small fragment of the
original antigen.
Antigen processing refers to the degradation of antigen
into peptide fragments, which become bound to major
histocompatibility complex (MHC) class I or class II
molecules (see Chapter 5). These are the critical fragments involved in triggering T cells. TCRs are sensitive
to the sequences of amino acids in the MHC molecule
peptide-binding groove rather than the conformational
determinants recognized by antibodies.
Antigen presentation plays a central role in initiating
and maintaining an appropriate immune response to

Co-stimulatory molecules are essential for T cell

activation. Molecules such as B7 (CD80/86) on the APC
bind to CD28 on the T cell to cause activation. Antigens
presented without co-stimulation usually induce T cell
anergy. Intercellular adhesion molecules also contribute to
the interaction between a T cell and an antigen-presenting
cell (APC). Interactions between intercellular cell adhesion
molecule-1 (ICAM-1) and leukocyte functional antigen-1
(LFA-1) and between CD2 and its ligands extend the
interaction between T cells and APCs.
CD4 binds to MHC class II and CD8 to MHC class I
molecules. These interactions increase the affinity of T cell
binding to the appropriate MHCantigen complex and
bring kinases to the TCR complex.
The highly ordered area of contact between the T cell
and APC is an immunological synapse.
T cell activation induces enzyme cascades, leading to
the production of interleukin-2 (IL-2) and the highaffinity IL-2 receptor on the T cell. IL-2 is required to
drive T cell division.
Antigen presentation affects the subsequent course of
an immune response. The immune system responds to
clues that an infection has taken place before responding
strongly to antigens.

antigen. The process is tightly controlled at several levels

as follows:
different types of antigen-presenting cell (APC) are
brought into play depending on the situation, dendritic
cells (DCs) being crucial for initiating responses;
a complex series of molecular interactions takes place to
ensure that small fragments of antigens are recognized
in a highly specific manner by T cells;
another level of control is exerted by co-stimulatory
molecules on APCs, resulting in T cell activation only
when appropriate, such as in an infection;
adhesion molecules on the interacting cells also
contribute to the stable binding of the cells, which
promotes effective antigen presentation;
signals from the cell surface are then transmitted by a
series of signal transduction pathways that regulate
gene expression in the nucleus;

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