Allospecific cytotoxic T lymphocytes recognize an H-2 peptide in the context of a murine major histocompatibility complex class I molecule

We have isolated cytotoxic T lymphocytes (CTL) preferentially reactive with the alpha 1 external domain of the H-2Ld antigen by selecting for T cells capable of recognizing a variant major histocompatibility complex (MHC) class I antigen sharing alpha 1 sequences with H-2Ld. Using these CTL, we demonstrate that a synthetic alpha 1 peptide corresponding to one of the helices derived from the H-2Ld molecule can be presented by a class I restriction element to reconstitute a CTL determinant borne by intact H-2Ld. Moreover, several other H-2L-reactive CTL generated independently were also able to recognize H-2Ld either as an intact alloantigen or as a peptide in conjunction with appropriate class I restriction elements. These data demonstrate that an H-2 peptide can reconstitute a CTL target structure and suggest that some alloreactive T cells in fact might be directed against allogeneic class I peptides in the context of a class I framework.