INVOLVEMENT OF P21RAS DISTINGUISHES POSITIVE AND NEGATIVE SELECTION IN THYMOCYTES

摘要: Small molecular weight GTP binding proteins of the ras family have been implicated in signal transduction from T cell antigen receptor (TCR). To test importance p21ras control thymocyte development, we generated mice expressing a dominant-negative protein (H-rasN17) lineage cells under lck proximal promoter. Proliferation thymocytes lck-H-rasN17 response to TCR stimulation was nearly completely blocked, confirming mediating TCR-derived signals mature CD4+8- or CD8+4- thymocytes. In contrast, some proceeded unimpaired CD4+8+ p21ras. Analysis development made doubly transgenic for H-Y-specific and demonstrated that antigen-specific negative selection occurs normally presence p21H-rasN17. Superantigen-induced vivo also unhindered H-rasN17 positive H-Y severely compromised by These observations demonstrate selection, two conceptually antithetical consequences stimulation, are biochemically distinguishable.