Cancer cells may escape from immune surveillance if they mask or otherwise modulate the surface expression of critical surface antigens. The following proposal is an in-depth cell biological and biochemical study of the biosynthesis and modulation anchored to the lipid bilayer by a glycophospholipid (GPL) attached to the C- terminus of a truncated form of the primary translation product. A family of Thy-1 negative lymphoma mutants produced by negative immunoselection has been show that representatives of groups A-C secrete anchor-deficient, hydrophilic forms of Thy-1 (see enclosed reprint and preprint). The proposed studies aim: I. To use wild-type cells to establish the subcellular site(s) of anchor addition, to set up a microsomal for in vitro anchor addition, and to learn how many lymphoma proteins bear a GPL. II. To use the mutant lymphomas for investigation of anchor biosynthetic lesions and for comparison with cells recovered from paroxysmal nocturnal hemoglobinuria (PNH) patients. III. To use the approach to transfection to anchor both Thy-1 and secretory proteins to the surface of CHO cells via a GPL anchor. Taken together, these studies will elucidate normal GPL anchor biosynthesis and evaluate the hypothesis that secretion of Thy-1 by the mutant cells is the result of lesions in the pathway of anchor biosynthesis.
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