Introduction

To protect the individual from foreign agents, such as viruses and bacteria, mammals have evolved a sophisticated system that allows them to distinguish self from non-self. Self/non-self discrimination was first demonstrated in mammals by the rejection of foreign tissue grafts in mice (Gorer, 1936; Snell, 1958; Klein, 1975). The genetic loci involved in graft rejection were subsequently mapped to a region on chromosome 17 (Klein, 1975), which became known as the major histocompatibility complex (MHC). The human MHC, also known as the human leukocyte antigen (HLA) system, is located on chromosome 6 (van Someren et al, 1974).

The MHC occupies some 3.5 megabase pairs (Mb) of the genome and, in humans, approximately 75 genes (many still of unknown function) have been identified in this region (Trowsdale, Ragoussis & Campbell, 1991). The organization of the MHC is reviewed in detail in Chapter 2. The complex is often divided into three different classes of gene: I, II and III. There are multiple class I loci but the classical ‘transplantation antigens’ fall into three positions termed HLA-A, HLA-B and HLA-C in humans. The class II genes, encoded in the HLA-D region, encode proteins that help regulate the immune response to different antigens (Fig. 1.1). In early experiments that studied the genetic control of immunity to certain protein antigens, the immune response, whether strong or weak, was found to depend on particular alleles at loci within the MHC.