The histocompatibility-2 (H-2) complex of the mouse consists of a series of closely linked loci on chromosome 17 which control glycoproteins and cell membrane antigens involved in a number of key functions in cellular and humoral immunity. In recent years the discovery of a cluster of genes controlling cell membrane antigens which are closely linked to H-2 but lie outside the traditionally defined H-2 complex, has prompted additional questions about the genetic organization of the chromosome area immediately adjacent (distal) to H-2. This chromosome segment is principally defined by loci controlling the Qa and TL antigens and has been called the T1a region. This proposal suggests two programs for expanding our knowledge of the genetic organization of the H-2 complex and the closely linked T1a region. The first approach involves an examination of crossing over in the T1a region with the intent of developing recombinant inbred strains which are identical at H-2 but differ with respect to a crossover point within the T1a region. This process will initially involve screening the offspring of (B10.G x B10.M)F1 hybrids for crossing over between H-2 (to the left of T1a) and a locus controlling isozymes of kidney catalase, Ce-2 (to the right of T1a). Such strains will be used for genetic mapping of T1a region traits and for additional serological and functional characterization of T1a gene products. These intra-T1a recombinant strains will be of particular use as a genetic resource for molecular analysis of this region by DNA cloning. In the second approach we will examine the genetic organization and immunological character of the S region of the H-2 complex. This will be accomplished by seeking genetic variation in the C2, C4 and B components of hemolytic complement for the purpose of understanding their genetic control and location.
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