Journal article

Cutting Edge: CD1a Tetramers and Dextramers Identify Human Lipopeptide-Specific T Cells Ex Vivo

Anne G Kasmar, Ildiko Van Rhijn, Kelly G Magalhaes, David C Young, Tan-Yun Cheng, Marie T Turner, Andre Schiefner, Ravi C Kalathur, Ian A Wilson, Mugdha Bhati, Stephanie Gras, Richard W Birkinshaw, Li L Tan, Jamie Rossjohn, John Shires, Soren Jakobsen, John D Altman, D Branch Moody

The Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2013

Abstract

Human CD1a mediates foreign Ag recognition by a T cell clone, but the nature of possible TCR interactions with CD1a/lipid are unknown. After incubating CD1a with a mycobacterial lipopeptide Ag, dideoxymycobactin (DDM), we identified and measured binding to a recombinant TCR (TRAV3/ TRBV3-1, KD of ≈100 μM). Detection of ternary CD1a/lipid/TCR interactions enabled development of CD1a tetramers and CD1a multimers with carbohydrate backbones (dextramers), which specifically stained T cells using a mechanism that was dependent on the precise stereochemistry of the peptide backbone and was blocked with a soluble TCR. Furthermore, sorting of human T cells from unrelated tuberculosis patients for br..

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Grants

Awarded by National Institutes of Health


Awarded by Nederlands Wetenschappelijk Onderzoek


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

This work was supported by grants from the Howard Hughes Medical Institute KwaZulu-Natal Research Institute for Tuberculosis and HIV (to A. G. K. and D. B. M.), the Harvard University Global Health Initiative (to A. G. K.), the Burroughs Wellcome Fund Program in Translational Research (to D. B. M.), as well as by National Institutes of Health Grants T-32 AI 007306-22, T-32 AR 007530-23, K08 AI089858 (to A. G. K.), R01 AI49313, R01 AR048632 (to D. B. M.), and R01 A1042266 (to I. A. W.) and a grant from the Nederlands Wetenschappelijk Onderzoek (Meervoud 836.08.001) (to I. V. R.). S. G. is supported by an Australian Research Council Future Fellowship. J.R. is supported by a National Health and Medical Research Council Australia Fellowship.