INCREASED FREQUENCY OF T-CELL RECEPTOR V-ALPHA-12.1 EXPRESSION ON CD8+ T-CELLS - EVIDENCE THAT V-ALPHA PARTICIPATES IN SHAPING THE PERIPHERAL T-CELL REPERTOIRE

The T cell receptor repertoire has a potential for vast diversity. However, this diversity is limited by the fact that the majority of thymocytes die as the repertoire is shaped by positive and negative selection events during development. Such thymic selection affecting TCR V-beta gene segment usage has been demonstrated in the mouse. However, similar data has not been forthcoming in man, and little is known about the role of the TCR alpha-chain in antigen/major histocompatibility complex (MHC) recognition in any species. Here, we used a monoclonal antibody recognizing the TCR V-alpha-12.1 gene product to assess the expression of this gene in the peripheral blood of man. In most individuals tested, the percentage of cells expressing V-alpha-12.1 was significantly higher in CD8+ T cells than in CD4+ T cells. That the V-alpha gene product itself was responsible for this increased expression in CD8+ T cells was underscored by the lack of substantial skewing of V-beta usage in the V-alpha-12.1-bearing T cells. Moreover, the skewed expression of V-alpha-12.1 was already present at birth, indicating that it was likely to be due to a developmental process rather than the result of exposure to environmental antigens. Based on the established role for CD8 in binding to class I MHC molecules, we suggest that increased expression of V-alpha-12.1 on CD8+ T cells points to a role for TCR's using V-alpha-12.1 in class I MHC/Ag recognition. These results indicate that V-alpha gene usage in the peripheral blood of man is not random, and they support a role for V-alpha as a participant in the self-MHC recognition process that shapes the TCR repertoire.