CONTROL OF THE RAT T-CELL RESPONSE TO RETROVIRAL AND BACTERIAL SUPERANTIGENS BY CLASS-II MHC PRODUCTS AND TCRB-V8.2 ALLELES

The in vitro response of unprimed rat T cells to retroviral and bacter ial superantigens (SAg) was analyzed with TCR V beta 8.2-, 8.5-, 10-, and 16-specific mAbs. Specific stimulation of V beta 8.2 and 8.5 CD4 c ells was observed in the response to Mls1(a), the retroviral SAg encod ed by integrated provirus Mtv-7 (Mtv-7 SAg), which was presented by mo use B cells or mouse fibroblasts transfected with DR1 genes and the Mt v-7 SAg. Additionally, a strong response of V beta 16 CD4 cells to an as yet unidentified mouse SAg was found. Only some of the bacterial SA g known to stimulate mouse and human T cells also activated rat lymph node cells. SEA, SEE, and TSST-1 stimulated rat T cells well; SEB, SEC 1, and SED did not. This defect was apparently a result of weak bindin g to rat MHC class II molecules because presentation by human MHC clas s II molecules restored T cell activation. Under these conditions, SEB stimulated V beta 8.2(+) and 8.5(+) CD4 and CD8 cells from Lewis rats . A comparison of several rat strains revealed an unresponsiveness to SEB or Mtv-7 SAg for V beta 8.2 cells from F344 and DA rats. Determina tion of the nucleotide sequences of the Tcrb-V8.2 of these strains rev ealed differences between SAg-responsive and SAg-unresponsive Tcrb-V8. 2 in seven amino acids, four of them located in the putative SAg conta ct site. The significance of these findings for the evolution of TCR-S Ag interactions is discussed.