The evolution of genes in the major histocompatibility complex

The mammalian major histocompatibility system (MHS) includes genes determining the structure of the classical major transplantation antigens (H-2K and H-2D), the I region-associated (Ia) antigens, and genes determining the structure level or both of the first four components of complement. In addition, the I region incudes a series of genes determining specific immune responsiveness to a wide variety of antigens - the Ir genes. The available evidence indicates that the K, D, and I gene products are cell surface glycoproteins that are structurally and perhaps functionally related. The multiple genes in this complex region apparently arose by a process of tandem gene duplication. There is some reason to believe that the murine MHS may have originated from genes in the T/t complex - a "supergene" near the centromere of the 17th mouse chromosome determining a series of steps in early embryonic development. Other evidence has led to the postulate that genes in the MHS have given rise to immunoglobulin structural genes by a process of translocation and further gene duplication. While these evolutionary relationships are speculative, it seems clear that the MHS determines a series of cell surface proteins that are intimately involved in cellular recognition and interaction, and in regulation of immune responsiveness by a new, nonimmunoglobulin recognition system.