Microbiology & Immunology - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/226

Filters

2012 - 2013 2
2
Reset filters

Settings
Statistics
Citations
Author: Godfrey, Dale × Author: Uldrich, Adam × Subject: repertoire ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    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.
  • Item
    Thumbnail Image
    Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells
    Reantragoon, Rangsima ; Corbett, Alexandra J. ; Sakala, Isaac G. ; Gherardin, Nicholas A. ; Furness, John B. ; CHEN, ZHENJUN ; Eckle, Sidonia B.G. ; Uldrich, Adam P. ; Birkinshaw, Richard W. ; Patel, Onisha ; KOSTENKO, LYUDMILA ; MEEHAN, BRONWYN ; KEDZIERSKA, KATHERINE ; Liu, Ligong ; Fairlie, David P. ; Hansen, Ted H. ; GODFREY, DALE I. ; ROSSJOHN, JAMIE ; MCCLUSKEY, JAMES ; KJER-NIELSEN, LARS (Rockefeller University Press, 2013)
    Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) alpha-chain, TRAV1-2-TRAJ33, and are activated by vitamin B metabolites bound by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. Understanding MAIT cell biology has been restrained by the lack of reagents to specifically identify and characterize these cells. Furthermore, the use of surrogate markers may misrepresent the MAIT cell population. We show that modified human MR1 tetramers loaded with the potent MAIT cell ligand, reduced 6-hydroxymethyl-8-D-ribityllumazine (rRL-6-CH2OH), specifically detect all human MAIT cells. Tetramer(+) MAIT subsets were predominantly CD8(+) or CD4(-)CD8(-), although a small subset of CD4(+) MAIT cells was also detected. Notably, most human CD8(+) MAIT cells were CD8 alpha(+)CD8 beta(-/lo), implying predominant expression of CD8 alpha alpha homodimers. Tetramer-sorted MAIT cells displayed a T(H)1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1-rRL-6-CH2OH tetramers detected CD4(+), CD4(-)CD8(-) and CD8(+) MAIT cells in V. 19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-beta repertoire, and although the majority of human MAIT cells expressed TRAV1-2-TRAJ33, some expressed TRAJ12 or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow precise phenotypic characterization of human and mouse MAIT cells and revealed unanticipated TCR heterogeneity in this population.