ISOLATION OF A CDNA-ENCODING THYMIC SHARED ANTIGEN-1 - A NEW MEMBER OF THE LY6 FAMILY WITH A POSSIBLE ROLE IN T-CELL DEVELOPMENT

We have previously characterized a novel mouse thymocyte marker, defin ed as thymic shared Ag-1 (TSA-1), present on both immature thymocytes and a subset of thymic medullary epithelial cells. MTS 35, a mAb speci fic for TSA-1, alters T cell differentiation when added to fetal thymi c organ cultures, suggesting TSA-1 may be important for T cell develop ment in the thymus. In this study, we describe the isolation of a cDNA encoding TSA-1 using transient expression of COS-7 cells and selectio n with MTS 35. The predicted amino acid sequence of this cDNA encodes a 15 to 17-kDa protein and the expressed protein is linked to the memb rane via a phosphatidylinositol moiety. TSA-1 is transcriptionally act ive at various levels in all organs examined, suggesting that its role is not solely intrathymic. TSA-1 shares amino acid sequence homology to the mouse Ly6 multigene family, epidermal growth factor-like recept ors, and to cobra venom neurotoxin. The Tsa-1 locus is located on chro mosome 15 linked to Ly6 on the mouse genome. We also examined the effe cts of MTS 35 in fetal thymic organ cultures repopulated with two subs ets of thymocytes representing defined stages of T cell development. O ur results suggest that TSA-1 may play a role during positive selectio n and the transition from CD4+CD8+ thymocytes to the mature CD4+CD8- a nd CD4-CD8+ subsets.