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An MHC Class Ib-Restricted TCR That Cross-Reacts with an MHC Class Ia Molecule¹

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322

TCR transgenic 6C5 T cells recognize an insulin B chain epitope presented by the nonclassical class I MHC molecule, Qa-1^b. Positive selection of these T cells was shown previously to require Qa-1^b. Despite dedicated specificity for Qa-1^b, 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-2^bxq 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-2^q mice, and specificity was mapped to D^q. Evidence was obtained for direct recognition of D^q, rather than indirect presentation of a D^q-derived peptide presented by Qa-1^b. Polyclonal CD8⁺ T cells from class Ia-deficient K^bD^b–/– 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.

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