Microbiology & Immunology - Research Publications

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Author: Godfrey, Dale × Author: Pellicci, Daniel × Start date: 2000 × Subject: crystal-structure ×

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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-restricted antigens by natural killer T cells
    Rossjohn, J ; Pellicci, DG ; Patel, O ; Gapin, L ; Godfrey, DI (NATURE PUBLISHING GROUP, 2012-12)
    Natural killer T (NKT) cells are innate-like T cells that rapidly produce a variety of cytokines following T cell receptor (TCR) activation and can shape the immune response in many different settings. There are two main NKT cell subsets: type I NKT cells are typically characterized by the expression of a semi-invariant TCR, whereas the TCRs expressed by type II NKT cells are more diverse. This Review focuses on the defining features and emerging generalities regarding how NKT cells specifically recognize self, microbial and synthetic lipid-based antigens that are presented by CD1d. Such information is vitally important to better understand, and fully harness, the therapeutic potential of NKT cells.