Microbiology & Immunology - Research Publications

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Author: Godfrey, Dale × Author: McPherson, Kirsty × Type: Journal Article ×

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    The molecular bases of δ/αβ T cell-mediated antigen recognition
    Pellicci, DG ; Uldrich, AP ; Le Nours, J ; Ross, F ; Chabrol, E ; Eckle, SBG ; de Boer, R ; Lim, RT ; McPherson, K ; Besra, G ; Howell, AR ; Moretta, L ; McCluskey, J ; Heemskerk, MHM ; Gras, S ; Rossjohn, J ; Godfrey, DI (ROCKEFELLER UNIV PRESS, 2014-12-15)
    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.
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    CD1d-lipid antigen recognition by the γδ TCR
    Uldrich, AP ; Le Nours, J ; Pellicci, DG ; Gherardin, NA ; McPherson, KG ; Lim, RT ; Patel, O ; Beddoe, T ; Gras, S ; Rossjohn, J ; Godfrey, DI (NATURE PUBLISHING GROUP, 2013-11)
    The T cell repertoire comprises αβ and γδ T cell lineages. Although it is established how αβ T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for γδ TCRs. We describe a population of human Vδ1(+) γδ T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a γδ TCR binds CD1d-α-galactosylceramide (α-GalCer). The γδ TCR docked orthogonally, over the A' pocket of CD1d, in which the Vδ1-chain, and in particular the germ line-encoded CDR1δ loop, dominated interactions with CD1d. The TCR γ-chain sat peripherally to the interface, with the CDR3γ loop representing the principal determinant for α-GalCer specificity. Accordingly, we provide insight into how a γδ TCR binds specifically to a lipid-loaded antigen-presenting molecule.