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

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. T he vast majority of CD8 ϩ T cells are selected in the thy-mus by classical MHC class Ia molecules encoded by the H-2K, H-2D, and H-2L genes. The T cell repertoire appears to have inherent germline-encoded specificity for MHC molecules (1), which is substantially edited through positive and negative selection mechanisms during T cell development in the thymus (2, 3). Selection mechanisms lead to a dedicated population of T cells that are restricted by self MHC molecules and retain a capacity to recognize foreign peptides. Positive selection ensures the survival of T cells with a low affinity or avidity for the specific selecting MHC molecules. T cells with a high affinity or avidity for self MHC-peptide complexes are then deleted during negative selection. Despite this specialized system of selection by self MHC, as much as 10% of the mouse polyclonal T cell repertoire can cross-react with allogeneic MHC molecules (4) (5). In addition to class Ia molecules, there are a large number of ␤ 2-microglobulin-associated nonclassical class I molecules encoded in the Q, T, and M regions, and at other MHC-unlinked loci in the genome (6). A few of these class Ib molecules, including Qa-1, H2-M3, and Qa-2 have been demonstrated to act as restricting elements for CD8 ϩ TCR␣␤ T cells. Only a small fraction of the CD8 ϩ T cell repertoire appears to result …