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  • Title: Co-receptor-independent signal transduction in a mismatched CD8+ major histocompatibility complex class II-specific allogeneic cytotoxic T lymphocyte.
    Author: Eshima K, Tachibana M, Suzuki H, Yamazaki S, Shinohara N.
    Journal: Eur J Immunol; 1997 Jan; 27(1):55-61. PubMed ID: 9021998.
    Abstract:
    The contribution of co-receptors in signal transduction upon T cell receptor (TCR)-mediated recognition of major histocompatibility complex (MHC) class II antigen by mature T lymphocytes expressing TCR derived from the apparently co-receptor-independent, I-Ak-specific allogeneic CD8+ CTL clone QM11 has been examined. Mature double-negative, CD8+ and CD4+ bulk T cell lines and clones expressing TCR(QM11) were developed from TCR(QM11) transgenic mice. All these T cells, irrespective of co-receptor expression, showed specific lytic activity on cells expressing I-Ak. Furthermore, co-receptorless mutants were obtained from a CD4+ and CD8+ clone. The responses of these co-receptorless mutants upon specific recognition of the alloantigen, as judged by cytolytic activity, granule exocytosis, lymphokine production, proliferation, and tyrosine phosphorylation of the zeta chain, were comparable to those of the original clones. Thus, the results proved the co-receptor independence of the recognition of I-Ak by TCR(QM11) and further indicated there is no indispensable unique signal transduced by co-receptors. However, when the amount of the available antigen was limited by anti-I-Ak antibody, the CD4+ T cell clone showed a remarkable resistance to the inhibition whereas the mismatched CD8+ clone was readily inhibitable. The anti-I-Ak-resistant component of the CD4+ clone showed dependency on the CD4 molecule. Taken collectively, the results indicate that the role played by a co-receptor molecule in mature T cells is purely quantitative amplification of the signal through the formation of a TCR/MHC/co-receptor ternary complex, and also indicate that the role of co-receptor molecules as TCR-independent adhesion molecules is at best minimal.
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