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

A. Kasmar; I. van Rhijn; T. Magalhaes; D.C. Young; T.Y. Cheng; M.T. Turner; A. Schiefner; R.C. Kalathur; I.A. Wilson; M. Bhati; S. Gras; R.W. Birkinshaw; L.L. Tan; J. Rossjohn; J. Shires; S. Jakobsen; J.D. Altman; D.B. Moody

doi:10.4049/jimmunol.1301660

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

A. Kasmar, I. van Rhijn, T. Magalhaes, D.C. Young, T.Y. Cheng, M.T. Turner, A. Schiefner, R.C. Kalathur, I.A. Wilson, M. Bhati, S. Gras, R.W. Birkinshaw, L.L. Tan, J. Rossjohn, J. Shires, S. Jakobsen, J.D. Altman, D.B. Moody^*

^*Corresponding author for this work

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Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	4499-4503
Number of pages	5
Journal	Journal of Immunology
Volume	191
Issue number	9
DOIs	https://doi.org/10.4049/jimmunol.1301660
Publication status	Published - 1 Nov 2013

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Kasmar, A., van Rhijn, I., Magalhaes, T., 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

@article{732d757bcfd94ea0916c60605c015499,

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

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.",

author = "A. Kasmar and {van Rhijn}, I. and T. Magalhaes and D.C. Young and T.Y. Cheng and M.T. Turner and A. Schiefner and R.C. Kalathur and I.A. Wilson and M. Bhati and S. Gras and R.W. Birkinshaw and L.L. Tan and J. Rossjohn and J. Shires and S. Jakobsen and J.D. Altman and D.B. Moody",

year = "2013",

month = nov,

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doi = "10.4049/jimmunol.1301660",

language = "English",

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Kasmar, A, van Rhijn, I, Magalhaes, T, Young, DC, Cheng, TY, Turner, MT, Schiefner, A, Kalathur, RC, Wilson, IA, Bhati, M, Gras, S, Birkinshaw, RW, Tan, LL, Rossjohn, J, Shires, J, Jakobsen, S, Altman, JD & Moody, DB 2013, 'Cutting Edge: CD1a Tetramers and Dextramers Identify Human Lipopeptide - Specific T Cells Ex Vivo', Journal of Immunology, vol. 191, no. 9, pp. 4499-4503. https://doi.org/10.4049/jimmunol.1301660

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T1 - Cutting Edge: CD1a Tetramers and Dextramers Identify Human Lipopeptide - Specific T Cells Ex Vivo

AU - Kasmar, A.

AU - van Rhijn, I.

AU - Magalhaes, T.

AU - Young, D.C.

AU - Cheng, T.Y.

AU - Turner, M.T.

AU - Schiefner, A.

AU - Kalathur, R.C.

AU - Wilson, I.A.

AU - Bhati, M.

AU - Gras, S.

AU - Birkinshaw, R.W.

AU - Tan, L.L.

AU - Rossjohn, J.

AU - Shires, J.

AU - Jakobsen, S.

AU - Altman, J.D.

AU - Moody, D.B.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

U2 - 10.4049/jimmunol.1301660

DO - 10.4049/jimmunol.1301660

M3 - Article

SN - 0022-1767

VL - 191

SP - 4499

EP - 4503

JO - Journal of Immunology

JF - Journal of Immunology

IS - 9

ER -

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

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