Chapter 6 - The Major Histocompatibility Complex

Abstract

In this chapter, we describe the genes of the major histocompatibility complex (MHC) and their role in immune responses. The MHC class I and II genes encode surface proteins that present peptides to T cells. The corresponding MHC class I and II proteins are heterodimers with highly variant N-terminal domains forming a peptide-binding site. MHC class I is expressed on almost all cells and generally presents endogenous peptides. MHC class II is expressed by APCs and generally presents exogenous peptides. MHC class I interacts with CD8 on Tc cells and CTLs, while MHC class II interacts with CD4 on naïve and effector Th cells. The MHC genes are polygenic, polymorphic and expressed codominantly. Syngeneic individuals have the same MHC genotype, while allogeneic individuals have different MHC genotypes. Differences in MHC alleles between individuals are largely responsible for transplant rejection and variations in responses to pathogens. In addition, expression of particular MHC alleles is linked to autoimmune disease predisposition.