Increased frequency of T cell receptor Vα12.1 expression on CD8+ T cells: Evidence that Vα participates in shaping the peripheral T cell repertoire

Abstract

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 Vβ 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 a chain in antigen/major histocompatibility complex (MHC) recognition in any species. Here, we used a monoclonal antibody recognizing the TCR Vα12.1 gene product to assess the expression of this gene in the peripheral blood of man. In most individuals tested, the percentage of cells expressing Vα12.1 was significantly higher in CD8+ T cells than in CD4+ T cells. That the Va gene product itself was responsible for this increased expression in CD8+ T cells was underscored by the lack of substantial skewing of Vβ usage in the Vα12.1-bearing T cells. Moreover, the skewed expression of Vα12.1 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 Vα12.1 on CD8+ T cells points to a role for TCR's using Vα12.1 in class I MHC/Ag recognition. These results indicate that Vα gene usage in the peripheral blood of man is not random, and they support a role for Vα as a participant in the self-MHC recognition process that shapes the TCR repertoire.