Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recognition of MHC + peptide complexes by TCRs is thought to involve a large surface formed by exposed residues from the bound peptide and from the alpha-helices of the MHC protein. This interaction appears to be essentially symmetrical in the positioning of the TCR relative to the MHC molecule. In this study the topology of HLA-B27 recognition by an alloreactive TCR, 64.8P, has been analyzed with a panel of site-specific mutants that have changes at multiple positions along the peptide binding site of HLA-B27. Abrogation of transfectant target cell lysis by CTL 64.8P was obtained only with some mutations in the peptide side chain binding pockets A and B, whereas little or no effect was observed with mutations outside these pockets. CTL 64.8P efficiently lysed murine transfectant cells, including HLA-B27+ RMA-S cells. Recognition of this latter transfectant was more efficient upon increased HLA-B27 expression at 26 degrees C. The uneven distribution of mutations affecting HLA-B27 allorecognition by CTL 64.8P strongly suggests an asymmetrical topology in the interaction of this TCR with HLA-B27, in which most of the binding energy is provided by contacts with HLA-B27 and/or peptide residues located close to pockets A and B, with little contribution from other areas of the MHC or peptide molecules. Its conservation in RMA-S cells further suggests that the epitope recognized by CTL 64.8P is either peptide-independent or requires any of a set of peptides having the same amino-terminal residues.
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PMID:Unusual topology of an HLA-B27 allospecific T cell epitope lacking peptide specificity. 751 Jul 42

The CD4 and CD8 molecules are involved in T cell differentiation and activation. Nevertheless, efficient thymic maturation of helper T cells has been shown in the absence of the CD4 molecule. These CD4-deficient helper T cells expressed alpha beta-TCR and were able to control Leishmania infections and to mediate Ab class switch. Using mice deficient for the CD8 alpha-chain, we investigated whether a similar cytotoxic T cell population was generated in the absence of the CD8 coreceptor. A CD8-deficient cytotoxic T cell population corresponding to the described CD4-deficient helper T cell population was virtually absent both functionally and physically. These results support the idea that thymic maturation is asymmetrical and strongly biased toward the helper phenotype.
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PMID:T cell development in CD8-/- mice. Thymic positive selection is biased toward the helper phenotype. 756 Oct 76