| Literature DB >> 20620942 |
Felix M Wensveen1, Klaas P J M van Gisbergen, Ingrid A M Derks, Carmen Gerlach, Ton N Schumacher, René A W van Lier, Eric Eldering.
Abstract
The adaptive immune system generates protective T cell responses via a poorly understood selection mechanism that favors expansion of clones with optimal affinity for antigen. Here we showed that upon T cell activation, the proapoptotic molecule Noxa (encoded by Pmaip1) and its antagonist Mcl-1 were induced. During an acute immune response against influenza or ovalbumin, Pmaip1(-/-) effector T cells displayed decreased antigen affinity and functionality. Molecular analysis of influenza-specific T cells revealed persistence of many subdominant clones in the Pmaip1(-/-) effector pool. When competing for low-affinity antigen, Pmaip1(-/-) TCR transgenic T cells had a survival advantage in vitro, resulting in increased numbers of effector cells in vivo. Mcl-1 protein stability was controlled by T cell receptor (TCR) affinity-dependent interleukin-2 signaling. These results establish a role for apoptosis early during T cell expansion, based on antigen-driven competition and survival of the fittest T cells. Copyright 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20620942 DOI： 10.1016/j.immuni.2010.06.005
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745