Photoaffinity antigens for human gammadelta T cells

Ghanashyam Sarikonda; Hong Wang; Kia-Joo Puan; Xiao-hui Liu; Hoi K Lee; Yongcheng Song; Mark D Distefano; Eric Oldfield; Glenn D Prestwich; Craig T Morita

doi:10.4049/jimmunol.181.11.7738

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Photoaffinity antigens for human gammadelta T cells

Journal article

Peer reviewed

Photoaffinity antigens for human gammadelta T cells

Ghanashyam Sarikonda, Hong Wang, Kia-Joo Puan, Xiao-hui Liu, Hoi K Lee, Yongcheng Song, Mark D Distefano, Eric Oldfield, Glenn D Prestwich and Craig T Morita

The Journal of immunology (1950), Vol.181(11), pp.7738-7750

12/01/2008

DOI: 10.4049/jimmunol.181.11.7738

PMCID: PMC2696061

PMID: 19017963

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Abstract

Vgamma2Vdelta2 T cells comprise the major subset of peripheral blood gammadelta T cells in humans and expand during infections by recognizing small nonpeptide prenyl pyrophosphates. These molecules include (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP), a microbial isoprenoid intermediate, and isopentenyl pyrophosphate, an endogenous isoprenoid intermediate. Recognition of these nonpeptide Ags is mediated by the Vgamma2Vdelta2 T cell Ag receptor. Several findings suggest that prenyl pyrophosphates are presented by an Ag-presenting molecule: contact between T cells and APC is required, the Ags do not bind the Vgamma2Vdelta2 TCR directly, and Ag recognition is abrogated by TCR mutations in CDRs distant from the putative Ag recognition site. Identification of the putative Ag-presenting molecule, however, has been hindered by the inability to achieve stable association of nonpeptide prenyl pyrophosphate Ags with the presenting molecule. In this study, we show that photoaffinity analogues of HMBPP, meta/para-benzophenone-(methylene)-prenyl pyrophosphates (m/p-BZ-(C)-C(5)-OPP), can crosslink to the surface of tumor cell lines and be presented as Ags to gammadelta T cells. Mutant tumor cell lines lacking MHC class I, MHC class II, beta(2)-microglobulin, and CD1, as well as tumor cell lines from a variety of tissues and individuals, will all crosslink to and present m-BZ-C(5)-OPP. Finally, pulsing of BZ-(C)-C(5)-OPP is inhibited by isopentenyl pyrophosphate and an inactive analog, suggesting that they bind to the same molecule. Taken together, these results suggest that nonpeptide Ags are presented by a novel-Ag-presenting molecule that is widely distributed and nonpolymorphic, but not classical MHC class I, MHC class II, or CD1.

Photochemistry

Mutation

Histocompatibility Antigens - genetics

Organophosphorus Compounds - immunology

Humans

Receptors, Antigen, T-Cell, gamma-delta - genetics

Organophosphorus Compounds - pharmacology

Hemiterpenes - chemistry

Hemiterpenes - pharmacology

Histocompatibility Antigens - immunology

Organophosphorus Compounds - chemistry

Receptors, Antigen, T-Cell, gamma-delta - immunology

Antigen Presentation - immunology

Antigen-Presenting Cells - immunology

Hemiterpenes - immunology

Antigens - chemistry

Organophosphates - pharmacology

Organophosphates - immunology

Cell Line, Tumor

Antigens - immunology

Organophosphates - chemistry

T-Lymphocytes - immunology

Antigen Presentation - drug effects

Antigens - pharmacology

Cell Line, Transformed

Details

Title: Subtitle: Photoaffinity antigens for human gammadelta T cells
Creators: Ghanashyam Sarikonda - Department of Internal Medicine, Division of Rheumatology, niversity of Iowa College of Medicine, Iowa City, IA 52242, USA
Hong Wang
Kia-Joo Puan
Xiao-hui Liu
Hoi K Lee
Yongcheng Song
Mark D Distefano
Eric Oldfield
Glenn D Prestwich
Craig T Morita
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.181(11), pp.7738-7750
DOI: 10.4049/jimmunol.181.11.7738
PMID: 19017963
PMCID: PMC2696061
NLM abbreviation: J Immunol
eISSN: 1550-6606
Grant note: R01 GM058842-10 / NIGMS NIH HHS AR45504 / NIAMS NIH HHS R01 AR045504-06 / NIAMS NIH HHS U54 AI057160-05S10027 / NIAID NIH HHS R01 CA113874-01 / NCI NIH HHS R01 GM058842 / NIGMS NIH HHS R01 AR045504 / NIAMS NIH HHS R01 GM058842-07 / NIGMS NIH HHS R01 AR045504-09 / NIAMS NIH HHS GM58442 / NIGMS NIH HHS R01 AR045504-11 / NIAMS NIH HHS R01 NS029632-17 / NINDS NIH HHS U54 AI057160 / NIAID NIH HHS R01 NS029632 / NINDS NIH HHS R01 CA113874-04 / NCI NIH HHS R01 GM058842-08 / NIGMS NIH HHS R01 NS029632-14 / NINDS NIH HHS R01 GM073216 / NIGMS NIH HHS R01 GM073216-27 / NIGMS NIH HHS R01 GM073216-26A1 / NIGMS NIH HHS R01 AR045504-08 / NIAMS NIH HHS NS29632 / NINDS NIH HHS R01 AR045504-10 / NIAMS NIH HHS R01 CA113874-03 / NCI NIH HHS R01 NS029632-16 / NINDS NIH HHS R01 AR045504-07 / NIAMS NIH HHS R01 CA113874 / NCI NIH HHS R01 GM073216-29 / NIGMS NIH HHS CA113874 / NCI NIH HHS R03 AR045095-04 / NIAMS NIH HHS R01 GM073216-28 / NIGMS NIH HHS R01 CA113874-02 / NCI NIH HHS AI057160 / NIAID NIH HHS GM073216 / NIGMS NIH HHS R01 GM058842-11 / NIGMS NIH HHS R01 NS029632-15 / NINDS NIH HHS R01 GM058842-09 / NIGMS NIH HHS
Language: English
Date published: 12/01/2008
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094585602771

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