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

• Published in: The Journal of immunology (1950) 2005-06, Vol.174 (12), p.7746-7752
• Main Authors: Reed-Loisel, Lisa M, Sullivan, Barbara A, Laur, Oskar, Jensen, Peter E
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Line, Transformed; Cell Line, Tumor; Cell Lineage - genetics; Cell Lineage - immunology; Clonal Deletion; Crosses, Genetic; H-2 Antigens - genetics; H-2 Antigens - immunology; H-2 Antigens - metabolism; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Mammary Tumor Virus, Mouse - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Superantigens - genetics; Superantigens - immunology; Superantigens - metabolism; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7746

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(b)D(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.