Homology of (murine) H–2 and (human) HLA with a chicken histocompatibility antigen

Abstract

THE major histocompatibility complex (MHC) is a cluster of genes controlling a variety of immunological and nonimmunological phenomena¹. Membrane-bound glycoprotein products of the MHC genes are of two classes: molecules of one class consist of 44,000 MW polypeptide chain which is non-covalently associated with a smaller (12,000) chain of β₂-microglobulin¹; molecules of the second class consist of two polypeptide chains of 33,000 and 28,000 MW¹. The MHC was originally discovered in the mouse², where it is referred to as the histocompatibility–2 or H–2 system³. Later, similar systems were described in man, rhesus monkey, chimpanzee, rat, dog, rabbit and guinea pig; and, in fact, may exist in most, if not all, mammalian species⁴. Furthermore, clusters of genes controlling graft rejection, mixed lymphocyte reaction (MLR), immune responsiveness, and complement activity have also been reported in the chicken⁵ and Xenopus⁶. It is tempting to speculate that these gene clusters controlling immune functions form a single evolutionary line from more primitive ancestral genes in lower vertebrates to the HLA complex in man and the H–2 complex in the mouse⁷. Proof of such a relationship exists for the MHC of man and mouse, where the H–2 and HLA systems show considerable amino acid sequence homology in both classes of molecules⁷. Because of the relative closeness of the two species (H–2 and HLA), homology is not surprising. We have investigated whether the homology extends to other vertebrate classes, such as birds: for example, is the chicken B system a true evolutionary homologue of H–2 or HLA?