Functional reprogramming of the primary immune response by T cell receptor antagonism |
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Authors: | Haribhai Dipica Edwards Brandon Williams Mary L Williams Calvin B |
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Affiliation: | Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. |
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Abstract: | The T cell receptor must translate modest, quantitative differences in ligand binding kinetics into the qualitatively distinct signals used to determine cell fate. Here, we use mice that express an endogenous T cell receptor (TCR) antagonist and an adoptive transfer system to examine the influence of TCR signal quality on the development of effector function. We show that activation of antigen-specific T cells in the presence of an antagonist results in a functional reprogramming of the primary immune response, marked by altered T cell homing, a failure to develop effector function, and ultimately clonal elimination by apoptosis. Importantly, antagonism does not block cell division, implying that the signals promoting clonal expansion and effector differentiation are distinct. |
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Keywords: | immune tolerance clonal deletion lymphocyte activation immunization T lymphocyte effector |
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