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Celebrating T Cell Diversity

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Science  08 Feb 2002:
Vol. 295, Issue 5557, pp. 933
DOI: 10.1126/science.295.5557.933b

The duration of signals emanating from the T cell receptor (TCR) is finely regulated; for example, by controlling TCR half-life, by posttranslational modification, and by the recruitment of inhibitory proteins.

Egen and Allison have found that the inhibitory protein cytotoxic T lymphocyte antigen-4 (CTLA-4) is recruited to the immunological synapse, in direct proportion to the strength of the TCR signal, where it acts to extinguish TCR-dependent signals. CTLA-4 in T cells that were cultured with antigen-presenting cells (APCs) bearing agonistic or weakly agonistic peptides moved toward microtubule-organizing centers close to the site of T cell-APC apposition. However, only T cells stimulated with the stronger agonist peptides moved CTLA-4 into the immune synapse at the plasma membrane. Thus the location of CTLA-4 depends on the strength of the TCR signal. Strong signals by a few T cells (that have high affinity for an antigen) could quickly lead to the proliferation of a subset of T cells at the expense of a diverse group of proliferating T cells with varied affinity for the antigen. By recruiting the inhibitor CTLA-4 to the immune synapse, the prolonged signaling that would be mediated by strongly agonistic antigens is attenuated, and weakly stimulated T cells can proliferate, maintaining the diversity of T cell-mediated responses. — JN

Immunity16, 23 (2002).

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