The molecular bases of δ/αβ T cell–mediated antigen recognition
| العنوان: | The molecular bases of δ/αβ T cell–mediated antigen recognition |
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| المؤلفون: | Kristy G McPherson, Jérôme Le Nours, Renate de Boer, Dale I. Godfrey, Stephanie Gras, James McCluskey, Sidonia B G Eckle, Daniel G. Pellicci, Adam P Uldrich, Mirjam H.M. Heemskerk, Lorenzo Moretta, Eric Chabrol, Fiona Ross, Amy R. Howell, Gurdyal S. Besra, R.T. Lim, Jamie Rossjohn |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | The Rockefeller University Press, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Models, Molecular, T cell, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Immunology, Molecular Sequence Data, chemical and pharmacologic phenomena, Galactosylceramides, Streptamer, Lymphocyte Activation, Article, 03 medical and health sciences, Jurkat Cells, 0302 clinical medicine, medicine, Immunology and Allergy, Cytotoxic T cell, Humans, IL-2 receptor, Amino Acid Sequence, Antigen-presenting cell, 030304 developmental biology, 0303 health sciences, biology, ZAP70, hemic and immune systems, Receptors, Antigen, T-Cell, gamma-delta, Natural killer T cell, Molecular biology, Lipids, Clone Cells, medicine.anatomical_structure, CD1D, biology.protein, Antigens, CD1d, Peptides, 030215 immunology |
| الوصف: | Godfrey, Rossjohn, and colleagues define a population of T cells in healthy humans that express T cell receptors (TCRs) comprised of δ variable gene segments fused to α joining and constant domains and paired with a variety of TCR-β chains. Functional and structural analyses reveal how components of αβ and γδ TCR gene loci combine to create T cells with unique patterns of antigen recognition. αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1+ 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 δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity. |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eba5b6ac9b53bc0d523a2b7918615009 http://europepmc.org/articles/PMC4267242 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eba5b6ac9b53bc0d523a2b7918615009 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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