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Cutting edge: CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo

Kasmar, A. G., Van Rhijn, I., Magalhaes, K. G., Young, D. C., Cheng, T.-Y., Turner, M. T., Schiefner, A., Kalathur, R. C., Wilson, I. A., Bhati, M., Gras, S., Birkinshaw, R. W., Tan, L. L., Rossjohn, Jamie, Shires, J., Jakobsen, S., Altman, J. D. and Moody, D. B. 2013. Cutting edge: CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo. The Journal of Immunology 191 (9) , pp. 4499-4503. 10.4049/jimmunol.1301660

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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 bright DDM-dextramer staining allowed recovery of T cells that were activated by CD1a and DDM. These studies demonstrate that the mechanism of T cell activation by lipopeptides occurs via ternary interactions of CD1a/Ag/TCR. Furthermore, these studies demonstrate the existence of lipopeptide-specific T cells in humans ex vivo.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RM Therapeutics. Pharmacology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 04 Jun 2017 06:31
URI: http://orca.cf.ac.uk/id/eprint/61496

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