WEAK POSITIVE SELECTION OF TRANSGENIC T-CELL RECEPTOR-BEARING THYMOCYTES - IMPORTANCE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II, T-CELL RECEPTOR AND CD4 SURFACE-MOLECULE DENSITIES

We have produced alpha-beta T cell receptor (TcR)-transgenic mice and studied MHC-dependent positive selection of T cells bearing this receptor. The alpha and beta-transgenes were isolated from an I-E(d)-restricted, CD4+ BALB/c (H-2d/d) T cell clone specific for a peptide consisting of the 91-101 residues of the lambda-2 immunoglobulin light chain of MOPC315. Mice which carry the transgenes on a BALB/c background, but with H-2d/d, H-2b/d or H-2b/b major histocompatibility complex (MHC) haplotypes, were investigated for TcR expression in thymocytes and peripheral T cells. The thymocytes expressing the transgene-encoded alpha-beta receptor are weakly positively selected when compared with previous findings in other TcR-transgenic mice models. Thus, alpha-beta thymocytes vary in their efficacy of being positively selected by their restriction element. Furthermore, the density of TcR and CD4 on thymocytes, as well as the density of I-E(d) molecules on thymic epithelial cells, appear critical for the extent of positive selection. A possible explanation is that the transgenic TcR has a marginal affinity for self-MHC molecules on thymic epithelium, and that this may be compensated for by an increase in the number of CD4/TcR/MHC ternary complexes forming between the maturing thymocyte and the cortical epithelial cells.