The second part of this chapter focuses on the MHC class I and II genes and their tremendous variability. The MHC molecules are encoded within a large cluster of genes that were first identified by their powerful effects on the immune response to transplanted tissues and were therefore called the major histocompatibility complex (MHC). There are several different MHC molecules in each class, and each of their genes is highly polymorphic, with many variants present in the population. MHC polymorphism has a profound effect on antigen recognition by T cells, and the combination of multiple genes and polymorphism greatly extends the range of peptides that can be presented to T cells in each individual and in populations as a whole, thus enabling individuals to respond to the wide range of potential pathogens they will encounter. The MHC also contains genes other than those for the MHC molecules; some of these genes are involved in the processing of antigens to produce peptide:MHC complexes.
The last part of the chapter discusses the ligands for unconventional classes of T cells. We will examine a group of proteins similar to MHC class I molecules that have limited polymorphism, some encoded within the MHC and others encoded outside the MHC. These so-called nonclassical MHC class I proteins serve various functions, some acting as ligands for γ:δ T-cell receptors and MAIT cells, or as ligands for NKG2D expressed by T cells and NK cells. In addition, we will introduce a special subset of α:β T cells known as invariant NKT cells that recognize microbial lipid antigens presented by these proteins.
The generation of α:β T-cell receptor ligands.
The major histocompatibility complex and its function.
Generation of ligands for unconventional T-cell subsets.
The generation of α:β T-cell receptor ligands.
The protective function of T cells depends on their recognition of cells harboring intracellular pathogens or that have internalized their products. As we saw in Chapter 4, the ligand recognized by an α:β T-cell receptor is a peptide bound to an MHC molecule and displayed on a cell surface. The generation of peptides from native proteins is commonly referred to as antigen processing, while peptide display at the cell surface by the MHC molecule is referred to as antigen presentation. We have already described the structure of MHC molecules and seen how they bind peptide antigens in a cleft, or groove, on their outer surface (see Sections 4-13 to 4-16). We will now look at how peptides are generated from the proteins derived from pathogens and how they are loaded onto MHC class I or MHC class II molecules.
and in triggering their effector functions to attack pathogen- infected cells.
The processing and presentation of pathogen-derived antigens has two distinct purposes: inducing the development of armed effector T cells, and triggering the effector functions of these armed cells at sites of infection. MHC class I molecules bind peptides that are recognized by CD8 T cells, and MHC class II molecules bind peptides that are recognized by CD4 T cells, a pattern of recognition determined by specific binding of the CD8 or CD4 molecules to the respective MHC molecules (see Section 4-18). The importance of this specificity of recognition lies in the different distributions of MHC class I and class II molecules on cells throughout the body. Nearly all somatic cells (except red blood cells) express MHC class I molecules. Consequently, the CD8 T cell is primarily responsible for pathogen surveillance and cytolysis of somatic cells. Also called cytotoxic T cells, their function is to kill the cells they recognize. CD8 T cells are therefore an important mechanism in eliminating sources of new viral particles and bacteria that live only in the cytosol, and thus freeing the host from infection.