C H A P T E R

7Antigen Presentation

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T CELLS RECOGNIZE PEPTIDE FRAGMENTS BOUND TO MHC MOLECULESAntigens recognized by T cells are degraded or processedin some way so that the determinant recognized by the T cell receptor (TCR) is only a small fragment of theoriginal antigen.

Antigen processing refers to the degradation of antigeninto peptide fragments, which become bound to majorhistocompatibility complex (MHC) class I or class IImolecules (see Chapter 5). These are the critical frag-ments involved in triggering T cells. TCRs are sensitive to the sequences of amino acids in the MHC moleculepeptide-binding groove rather than the conformationaldeterminants recognized by antibodies.

Antigen presentation plays a central role in initiatingand maintaining an appropriate immune response to

antigen. The process is tightly controlled at several levelsas follows: different types of antigen-presenting cell (APC) are

brought into play depending on the situation, dendriticcells (DCs) being crucial for initiating responses;

a complex series of molecular interactions takes place toensure that small fragments of antigens are recognizedin a highly specific manner by T cells;

another level of control is exerted by co-stimulatorymolecules on APCs, resulting in T cell activation onlywhen appropriate, such as in an infection;

adhesion molecules on the interacting cells alsocontribute to the stable binding of the cells, whichpromotes effective antigen presentation;

signals from the cell surface are then transmitted by aseries of signal transduction pathways that regulategene expression in the nucleus;

SUMMARY

T cells recognize peptide fragments that have been processed and become bound to majorhistocompatibility complex (MHC) class I or IImolecules. These MHCantigen complexes are presented at the cell surface.

MHC class I molecules associate with endogenouslysynthesized peptides, binding to peptides produced by degradation of the cells internal molecules.This type of antigen processing is carried out byproteasomes (which cleave the proteins) and transporters(which take the fragments to the endoplasmic reticulum [ER]).

MHC class II molecules bind to peptides producedfollowing the breakdown of proteins that the cell hasendocytosed. The peptides produced by degradation ofthese external antigens are loaded onto MHC class IImolecules in a specialized endosomal compartment called MIIC.

Cross-presentation allows APCs to acquire antigens frominfected cells. A specialized pathway allows the acquisitionof antigens from infected cells by APCs. This pathway,called cross-presentation, allows the display of exogenousantigens by MHC class I molecules.

Co-stimulatory molecules are essential for T cellactivation. Molecules such as B7 (CD80/86) on the APCbind to CD28 on the T cell to cause activation. Antigenspresented without co-stimulation usually induce T cellanergy. Intercellular adhesion molecules also contribute tothe interaction between a T cell and an antigen-presentingcell (APC). Interactions between intercellular cell adhesionmolecule-1 (ICAM-1) and leukocyte functional antigen-1(LFA-1) and between CD2 and its ligands extend theinteraction between T cells and APCs.

CD4 binds to MHC class II and CD8 to MHC class Imolecules. These interactions increase the affinity of T cellbinding to the appropriate MHCantigen complex andbring kinases to the TCR complex.

The highly ordered area of contact between the T celland APC is an immunological synapse.

T cell activation induces enzyme cascades, leading tothe production of interleukin-2 (IL-2) and the high-affinity IL-2 receptor on the T cell. IL-2 is required todrive T cell division.

Antigen presentation affects the subsequent course ofan immune response. The immune system responds toclues that an infection has taken place before respondingstrongly to antigens.