IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

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The long-term objective of the proposed research is to learn what the avian major histocompatibility complex (MHC) can tell us about the evolution of the MHC gene complex and the means by which this MHC confers disease resistance. The proposed study provides an opportunity to contrast the strucutre of a non-mammalian MHC, the B system of the chicken, with the MHCs of mouse and man. It is already known that one B system subregion, the B-G subregion, encodes antigens which are differrent from known gene products associated with the MHC of mammals. While these antigens are highly polymorphic and their genes tightly-linked with those of the class I and class II antigens encoded within the B system, they are clearly different from all ohter MHC-encoded molecules. partial sequence data derived from a B-B cDNa clone isolated in this labe indicates that the B-G antigens contain a domain more closely similar to immunoglobulin and T-cell receptor variable region domains (recognition domains) than to Ig-constant region domains such as those found within class I and class II antigens. Another important aspect of the B system is the particularly strong association found between the presence of the B-F/B-L subregion genes and resistance to Marek's disease, a herpesvirus-induced lymphoma. Hence, the B system provides a model in which to study the relationship between the MHC and viral disease when suitable reagents become available. The specific aims are 1) to complete a structural analysis of the B-G21 antigens, produce a restriction enzyme map of the B-G gubregion and link B-G to the B-F and B-L subregions; 2) to undertake molecular cloning of B-F21 and B-L21 genes and complete a similar molecular genetic analysis of these B subregions which encode the avian class I and class II-like gene counterparts, and 3) we would like to begin to apply the information learned in the present study to the investigation of the process of infection and tumorigenesis caused by Marek's disease virus.