Using chicken class I sequences to understand how xenoantibodies crossreact with MHC-like molecules in nonmammalian vertebrates

Abstract

In an attempt to understand the evolutionary history of the major histocompatibility complex, we have characterized crossreactive molecules from nonmammalian vertebrates using rabbit antisera and monoclonal antibodies to mammalian and chicken MHC molecules. By this analysis, some chains of these heterodimers evolve more slowly than others, and interdomain contact sites evolve more slowly than surface residues. The antibodies to human MHC molecules crossreacted with amphibians much better than reptiles, the reverse was true for the antibodies to chicken MHC molecules, while neither crossreacted with recognizable molecules in fish. We then analyzed a chicken class I heterodimer in detail, and found that homologous domains have different rates of evolution, that most (but not all) interdomain and intradomain contacts are conserved or invariant, that the surface residues are quite diverged, but that patches of invariant residues occur in areas thought to interact with other molecules. Some of the domains are encoded by exons very rich in guanine and cytosine, to the point of affecting the amino acid composition relative to mammals. We present a very speculative model, in which the antigenic similarities of reptile and bird MHC molecules compared to mammals and amphibians are due to this high content of guanine and cytosine, and this in turn is due to the presence of these genes on microchromosomes. Finally, we try to explain the compressed nature of chicken immunoglobulin loci as another consequence of location on microchromosomes. © 1991 by the American Society of Zoologists.