Structural highlights
Publication Abstract from PubMedalphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50% of all Vdelta1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity. The molecular bases of delta/alphabeta T cell-mediated antigen recognition.,Pellicci DG, Uldrich AP, Le Nours J, Ross F, Chabrol E, Eckle SB, de Boer R, Lim RT, McPherson K, Besra G, Howell AR, Moretta L, McCluskey J, Heemskerk MH, Gras S, Rossjohn J, Godfrey DI J Exp Med. 2014 Dec 15;211(13):2599-615. doi: 10.1084/jem.20141764. Epub 2014 Dec, 1. PMID:25452463[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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