Microbiology & Immunology - Research Publications

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Author: Godfrey, Dale × Author: Uldrich, Adam × Type: Journal Article × Subject: CD1d ×

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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.
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    Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor
    Patel, O ; Pellicci, DG ; Gras, S ; Sandoval-Romero, ML ; Uldrich, AP ; Mallevaey, T ; Clarke, AJ ; Le Nours, J ; Theodossis, A ; Cardell, SL ; Gapin, L ; Godfrey, DI ; Rossjohn, J (NATURE PUBLISHING GROUP, 2012-09)
    Natural killer T cells (NKT cells) are divided into type I and type II subsets on the basis of differences in their T cell antigen receptor (TCR) repertoire and CD1d-antigen specificity. Although the mode by which type I NKT cell TCRs recognize CD1d-antigen has been established, how type II NKT cell TCRs engage CD1d-antigen is unknown. Here we provide a basis for how a type II NKT cell TCR, XV19, recognized CD1d-sulfatide. The XV19 TCR bound orthogonally above the A' pocket of CD1d, in contrast to the parallel docking of type I NKT cell TCRs over the F' pocket of CD1d. At the XV19 TCR-CD1d-sulfatide interface, the TCRα and TCRβ chains sat centrally on CD1d, where the malleable CDR3 loops dominated interactions with CD1d-sulfatide. Accordingly, we highlight the diverse mechanisms by which NKT cell TCRs can bind CD1d and account for the distinct antigen specificity of type II NKT cells.