3r06

Publication Abstract from PubMed

Native and non-native ligands of the T cell receptor (TCR), including antibodies, have been proposed to induce signaling in T cells via intra- or intersubunit conformational rearrangements within the extracellular regions of TCR complexes. We have investigated whether any signatures can be found for such postulated structural changes during TCR triggering induced by antibodies, using crystallographic and mutagenesis-based approaches. The crystal structure of murine CD3epsilon complexed with the mitogenic anti-CD3epsilon antibody 2C11 enabled the first direct structural comparisons of antibody-liganded and unliganded forms of CD3epsilon from a single species, which revealed that antibody binding does not induce any substantial rearrangements within CD3epsilon. Saturation mutagenesis of surface-exposed CD3epsilon residues, coupled with assays of antibody-induced signaling by the mutated complexes, suggests a new configuration for the complex within which CD3epsilon is highly exposed and reveals that no large new CD3epsilon interfaces are required to form during antibody-induced signaling. The TCR complex therefore appears to be a structure that is capable of initiating intracellular signaling in T cells without substantial structural rearrangements within or between the component subunits. Our findings raise the possibility that signaling by native ligands might also be initiated in the absence of large structural rearrangements in the receptor.

T cell receptors are structures capable of initiating signaling in the absence of large conformational rearrangements.,Fernandes RA, Shore DA, Vuong MT, Yu C, Zhu X, Pereira-Lopes S, Brouwer H, Fennelly JA, Jessup CM, Evans EJ, Wilson IA, Davis SJ J Biol Chem. 2012 Apr 13;287(16):13324-35. doi: 10.1074/jbc.M111.332783. Epub, 2012 Jan 19. PMID:22262845^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.