Genes of the Major Histocompatibility Complex

Abstract

Since the beginning of this century the curious nature of tissue rejection has intrigued investigators. It was no later than 1936 when Peter Gorer clearly articulated the existence of the MHC using transplanted tumors. Gorer’s work was the culmination of efforts to show that the rejection of transplanted tumor cells in mice involved a set of linked genetic loci, or histocompatibility genes. The term major histocompatibility complex or MHC, evolved from observations that rejection responses could be vigorous or mild, i.e., there were strong and weak histocompatibility loci, or, conversely, that there were major and minor histocompatibility antigens. As it is understood today, the MHC might simply be described as a collection of genes that encode immunologically relevant molecules, particularly those involved in cell-mediated T-lymphocyte immunity. The most fundamental elements of the MHC are a set of highly polymorphic genes that encode molecules involved in the presentation of antigenic peptides to αβ and perhaps γδ T lymphocytes. The extreme polymorphism of these so-called class I and class II genes facilitates display of myriad different antigenic peptides, a repertoire that must vary among different individuals in a population in order to protect from catastrophic disease. Genes encoding functionally diverse molecules such as TNF, LMP, and TAP (see Chapter 2) are also incorporated into the MHC gene cluster, suggesting perhaps a long evolutionary existence of the MHC in the vertebrate immune system. Although it is tempting to speculate that the MHC is a central feature in the evolution of vertebrate immunity, it must be remembered that only about 0.1% of vertebrate species have been investigated. Nonetheless, in all cases there exist MHC regions that share some degree of similarity. In this chapter we provide a brief overview of the MHC by way of discussing the genes and protein products of the class I and II regions. Immune response genes present in the class III region are discussed elsewhere (see chapters on antigen presentation and cytokines).