An MHC Class Ib-Restricted TCR That Cross-Reacts with an MHC Class Ia Molecule

Abstract

TCR transgenic 6C5 T cells recognize an insulin B chain epitope presented by the nonclassical class I MHC molecule, Qa-1b. Positive selection of these T cells was shown previously to require Qa-1b. Despite dedicated specificity for Qa-1b, evidence presented in the current study indicates that 6C5 T cells can cross-recognize a classical class I molecule. Clonal deletion was observed unexpectedly in 6C5.H-2bxq mice, which do not express I-E MHC class II molecules and thus should not be subject to superantigen-mediated negative selection. 6C5 T cells were observed to respond in vivo and in vitro to spleen cells from allogeneic H-2q mice, and specificity was mapped to Dq. Evidence was obtained for direct recognition of Dq, rather than indirect presentation of a Dq-derived peptide presented by Qa-1b. Polyclonal CD8+ T cells from class Ia-deficient KbDb−/− mice reacted in vitro to allogeneic spleen cells with an apparent frequency comparable to conventional class Ia-restricted T cells. Our results provide a clear example of a Qa-1-specific TCR that can cross-react with a class Ia molecule and evidence supporting the idea that this may be a common property of T cells selected by class Ib molecules.