While some major histocompatibility complex (Mhc) class Ib and class I-related molecules do present special antigens from infectious organisms to T cells, recent years have highlighted other functions in mouse and man, such as sending inhibitory signals to natural killer cells, regulating iron and immunoglobulin metabolism, and subtle roles in embryogenesis and development. The mouse Mhc contains more than 50 class Ib genes, distributed over the H2-Q,-T and -M regions, but existing maps leave several gaps, and the genes have not all been sequenced, so their exact number and status are unknown. Complete maps of the class Ib regions will be made from strain C57BL/6 (H2b), based on an 8 megabase YAC contig covering the entire Mhc, and strain 129 (H2bc), the strain of choice for creating knock-out models. For comparison, newly defined H2-Q genes of the H2p haplotype will be sequenced. A systematic catalog of the number, status, and relationship of the class Ib genes, and permanent DNA resource from two commonly used mouse strains will facilitate the design and evaluation of experiments addressing the function of class Ib genes. The H2-M region contains 21 class Ib gene sequences; 10 have full-length open reading frames, and five of these belong to the M10 family. M2 and M10 itself will be analysed by a general approach, applicable to any new class I gene. M2 is transcribed at levels detectable in Northern blots, whereas the M10 family is nearly silent. Their polymorphism will be determined among divergent mouse Mhc haplotypes and in the rat. M2 and M10 proteins will be expressed whole and in chimeric constructs and used to prepare antibodies to determine the expression pattern of the proteins in normal mice. The ability of M2 and M10 to bind 2m and peptides and to interact with CD8 and TAP will be tested, and cells with receptors for M2 and M10 will be stained and isolated with tetramers of these proteins.
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