@article {11843, title = {Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.}, journal = {Immunity}, volume = {27}, year = {2007}, month = {2007 Nov}, pages = {735-50}, abstract = {

The thymus generates major histocompatibility complex (MHC)-restricted alphabetaT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that MHC specificity might be imposed on a broader alphabetaTCR repertoire during thymic selection by CD4 and CD8 coreceptors that bind and effectively sequester the tyrosine kinase Lck, thereby preventing T cell receptor (TCR) signaling by non-MHC ligands that do not engage either coreceptor. This hypothesis predicts that, in coreceptor-deficient mice, alphabeta thymocytes would be signaled by non-MHC ligands to differentiate into alphabetaT cells lacking MHC specificity. We now report that MHC-independent alphabetaT cells were indeed generated in mice deficient in both coreceptors as well as MHC ("quad-deficient" mice) and that such mice contained a diverse alphabetaT cell repertoire whose MHC independence was confirmed at the clonal level. We conclude that CD4 and CD8 coreceptors impose MHC specificity on a broader alphabetaTCR repertoire during thymic selection by preventing thymocytes from being signaled by non-MHC ligands.

}, keywords = {Animals, Antigens, CD4, Antigens, CD8, Blotting, Northern, Cell Differentiation, Flow Cytometry, Fluorescent Antibody Technique, Immunoprecipitation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Major Histocompatibility Complex, Mice, Mice, Transgenic, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Thymus Gland}, author = {Van Laethem, Francois and Sarafova, Sophia D and Park, Jung-Hyun and Tai, Xuguang and Pobezinsky, Leonid and Guinter, Terry I and Adoro, Stanley and Adams, Anthony and Sharrow, Susan O and Feigenbaum, Lionel and Singer, Alfred} }