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

Anne 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 William Birkinshaw, Li Lynn Tan, Jamie Rossjohn, John Shires, Soren Jakobsen, John D Altman, D Branch Moody

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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 approximately 100 muM). 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.
Original languageEnglish
Pages (from-to)4499 - 4503
Number of pages5
JournalJournal of Immunology
Volume191
Issue number9
DOIs
Publication statusPublished - 2013

Cite this

Kasmar, A., 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, J., Shires, J., Jakobsen, S., Altman, J. D., & Moody, D. B. (2013). Cutting Edge: CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo. Journal of Immunology, 191(9), 4499 - 4503. https://doi.org/10.4049/jimmunol.1301660