Among the more remarkable features of the MHC is the extensive structural diversity present both in the organization of gene clusters within the class I and class II multigene families and in molecules. Many lines of evidence indicate that structural diversity is reflected in functional diversity among the MHC glycoproteins. Understanding MHC diversity is one key to deciphering how the immune system functions. The long-term goal of the presented studies is to determine the structure and origin of MHC diversity and to relate this diversity to immune function.
The specific aims of this proposal are: 1) to determine whether there exists conserved genes with potential functional significance within the T1 region of the murine MHC; 2) to characterize the extent of the deletion within the Q region of the f-haplotype and establish its frequency in wild populations; 3) to determine the nucleotide sequence for all the uncharacterized K and D loci among the commonly studied inbred lines as well as for a select group of members of different wild mouse species; 4) to determine whether a previously identified copy mechanism that generates sequence diversity at the K and D loci introduces random mutations during the copy event; 5) to develop a molecular genetically-based approach to the analysis of the occurrence of spontaneous MHC mutants within mouse lines; and 6) to establish a cell culture system that permits the investigation of the genetic mechanisms driving gene conversion-like events among MHC genes.
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