Projects per year
Abstract
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.
Original language | English |
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Journal | The Journal of Experimental Medicine |
DOIs | |
Publication status | Published - 1 Dec 2014 |
Bibliographical note
© 2014 Pellicci et al.Fingerprint
Dive into the research topics of 'The molecular bases of δ/αβ T cell-mediated antigen recognition'. Together they form a unique fingerprint.Projects
- 1 Finished
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Design, synthesis, and assessment of specific iNKT cell agonists for clinical applications
Besra, D. (Principal Investigator), Cox, L. (Co-Investigator), Cunningham, A. (Co-Investigator) & Lammas, T. (Co-Investigator)
1/03/12 → 29/02/16
Project: Research Councils