The immune system of higher vertebrates provides mechanisms of defense against a variety of antigens and rapidly evolving infectious agents. Almost all immune responses involve T-lymphocytes, cells clonally expressing a variable antigen receptor that interacts with processed peptide antigens bound to either class I or class II Major Histocompatibility Complex (MHC) molecules. Multiple, highly polymorphic MHC loci are expressed and they differ between species. It is hypothesized that this provides diversification in T cell responsiveness. Moreover, there is evidence that selection based upon the prevailing requirement for T cell immunity can act to introduce new alleles and inactivate old ones. The class I genes are particularly active in this regard. The best characterized MHCs, those of humans and mice, show such tremendous diversification that they provide little understanding of short range evolution. In this investigation class I MHC genes and polymorphism in ape species, closely related to humans, will be analyzed. This will allow the fate of genes and alleles over periods of 5 to 20 million years to be assessed, provide further understanding of mutational events and a perspective from which to assess HLA polymorphism and its relationship to disease. Methods will be developed for cloning class I HLA obtained from soft tissues of individuals, dated at 7500 years old and well-preserved in an acidic lake in Florida. The sequences of these alleles will be compared to those found in contemporary human, including Amerindian, populations. The phylogenetic origins and diversity of class I MHC heavy chains will be investigated. A polymerase chain-based method has been used to identify and obtain probes for class I genes in fish, reptiles and amphibians. The class I genes and polymorphism of selected species will be characterized and compared to their homologues in mammals and birds. This information will enable strategies for the examination of invertebrate species for class I genes to be designed.
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