The immune system functions to maintain the integrity of the body by recognition and elimination of foreign material and accordingly must distinguish between self and non-self. Cell surface molecules on leukocytes mediate important interactions between these cells and their environment. Defining the function of leukocyte cell surface glycoproteins in molecular terms is one of the important tasks facing immunologists today. The long term objective of this application is to contribute to our understanding of the immune system by investigating the structure/function and regulation of T200; a family of cell surface glycoproteins found on all leukocyte but with a restricted distribution to hematopoietic cells. Members of this family vary a cell-type-specific pattern which is due to differential exon splicing of at least three exons. The glycoprotein is composed of an amino-terminal exterior domain of 400-550 amino acids and a cytoplasmic domain of 700 amino acids.
The specific aims of this project are to determine the extent of the variation in this family by examining different leukocyte populations and lymphoid tissues by northern blot analysis and in situ hybridization, probing separately with the three differentially spliced exons. The function of T200 glycoprotein will be investigated by using gene transfer to establish expression systems in lymphocyte cell lines for which functional assays are available. The regulation of this abundantly expressed molecule will be investigated by determining the genomic structure and examining the 5' upstream region for promoter and enhancer activity.
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