4WO4

The molecular bases of Delta/Alpha beta T cell-mediated antigen recognition.

Summary for 4WO4

• Entry DOI: 10.2210/pdb4wo4/pdb
• Related: 4WNQ
• Descriptor: Antigen-presenting glycoprotein CD1d, Beta-2-microglobulin, TCR variable DELTA 1 CHAIN and TCR constant Alpha, ... (9 entities in total)
• Functional Keywords: immunity, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 96145.11

Authors

Pellicci, D.G.,Uldrich, A.P.,Le Nours, J.,Ross, F.,Chabrol, E.,Eckle, S.B.G.,de Boer, R.,Lim, R.T.,McPherson, K.,Besra, G.,Howell, A.R.,Moretta, L.,McCluskey, J.,Heemskerk, M.H.M.,Gras, S.,Rossjohn, J.,Godfrey, D.I. (deposition date: 2014-10-15, release date: 2014-11-26, Last modification date: 2024-10-23)

Primary citation

Pellicci, D.G.,Uldrich, A.P.,Le Nours, J.,Ross, F.,Chabrol, E.,Eckle, S.B.,de Boer, R.,Lim, R.T.,McPherson, K.,Besra, G.,Howell, A.R.,Moretta, L.,McCluskey, J.,Heemskerk, M.H.,Gras, S.,Rossjohn, J.,Godfrey, D.I.
The molecular bases of delta / alpha beta T cell-mediated antigen recognition.
J.Exp.Med., 211:2599-2615, 2014

PubMed 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.

PubMed: 25452463
DOI: 10.1084/jem.20141764

Experimental method

X-RAY DIFFRACTION (2.5 Å)