Molecular Genetics of the HLA Region

The major histocompatibility complex (MHC), the HLA region in humans and H-2 in mouse, has been the subject of such intensive study for the last decade that several books have been devoted to this subject alone (for example, Receptors and Recognition Series B, Volume 13). Initial interest was spurred by the role of the MHC in transplantation rejection and by the discovery of very high levels of polymorphism at several loci in this region. Genetic studies on the MHC extend from the population level to nucleotide sequences. Population studies have contributed to anthropology indicating racial and geographic origins. They have also uncovered disease associations with particular antigens and antigenic combinations. Studies at the whole-organism level have led to an understanding of the rules of tissue transplantation and to the discovery of genes in the MHC which regulate immune responses and produce complement components. Cellular studies have defined the role of these MHC products in controlling cellular interactions in the immune response both in T cell killing (class I products or classical histocompatibility antigens) and in lymphocyte—lymphocyte and lymphocyte—accessory cell interaction (class II products or la antigens). This regulatory role of the MHC products has prompted the suggestion that the complement components (class III products) may also have a regulatory role in cell—cell interaction in the immune response.