T Cell Receptor Selection by and Recognition of Two Class I Major Histocompatibility Complex-restricted Antigenic Peptides That Differ at a Single Position By Jean-Laurent Casanova,* Frtdtric Martinon,~ H61~ne Gournier

Summary Peptides derived from HLA-Cw3 and HLA-A24 within region 170-179 differ by a single substitution, at position 173, and are both presented by the dass I major histocompatibility complex molecule H-2K a for recognition by routine cytolytic T lymphocytes (CTLs). As a first approach to understand the way T cell receptors (TCRs) intact with the HLA peptides, we have analyzed the TCR selection by, and recognition of, the two HLA antigenic sites. First, we have compared the TCR repertoires selected by HLA-Cw3 and HLA-A24, not only by sequencing the TCRs carried by CTL clones isolated and grown in vitro, but also by analyzing the TCRs expressed in vivo by peritoneal exudate lymphocytes from immune animals. Second, we have compared the TCR crossrecognition of HLA-A24 by CTLs selected by HLA-Cw3 with that of HLA-Cw3 by CTLs selected by HLA-A24. The combined analysis of TCR selection by and recognition of these two related HLA antigenic sites provides evidence that the TCR/3 junctional regions interact with the amino-terminal part of the HLA peptides.