The overall goal of this grant proposal is to understand the role of class Ib genes of the Q and T regions of the mouse major histocompatibility complex. One of the major functions of class Ia molecules is known -- these molecules aid in the presentation of viral peptide to cytotoxic T cell. However, the exact roles of other class I molecules especially those encoded by the Q and T regions are largely unknown. In this grant proposal, we will be investigating the hypothesis that some of these class Ib molecules may have unique roles in the immune responses in particular, their function may correlate with their unusual pattern of expression in tissues such as the intestinal epithelium. We have five specific aims: (1) We will investigate the expression of class I genes in the intestinal epithelium. Both cell lines and fresh tissues will be used to analyze class I gene expression and regulation. (2) We will determine the fine genetic structure of the T region in several prototype strains. Cosmid and YAC libraries will be used to make contig maps of the T region in several haplotypes. (3) We will continue to maintain and characterize the Q and T region congenic strains. These will be freely distributed to interested investigators. (4) We will investigate the expression of class I genes that are predominantly expressed in the intestinal epithelium. Antisera will be made and cell surface expression will be investigated. (S) We will examine the boundary region between the Q and T region. Functional genes will be identified and cloned. The genetic material between the Q and T regions will be isolated on overlapping cosmids.
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