Structural features of nonpeptide prenyl pyrophosphates that determine their antigenicity for human gamma delta T cells

Craig T Morita; Hoi K Lee; Hong Wang; Hongmin Li; Roy A Mariuzza; Yoshimasa Tanaka

doi:10.4049/jimmunol.167.1.36

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Structural features of nonpeptide prenyl pyrophosphates that determine their antigenicity for human gamma delta T cells

Journal article

Peer reviewed

Structural features of nonpeptide prenyl pyrophosphates that determine their antigenicity for human gamma delta T cells

Craig T Morita, Hoi K Lee, Hong Wang, Hongmin Li, Roy A Mariuzza and Yoshimasa Tanaka

The Journal of immunology (1950), Vol.167(1), pp.36-41

07/01/2001

DOI: 10.4049/jimmunol.167.1.36

PMID: 11418629

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Abstract

Human Vgamma2Vdelta2(+) T cells proliferate in vivo during many microbial infections. We have found that Vgamma2Vdelta2(+) T cells recognize nonpeptide prenyl pyrophosphates and alkylamines. We now have defined structural features that determine the antigenicity of prenyl pyrophosphates by testing synthetic analogs for bioactivity. We find that the carbon chain closest to the pyrophosphate moiety plays the major role in determining bioactivity. Changes in this area, such as the loss of a double bond, abrogated bioactivity. The loss of a phosphate from the pyrophosphate moiety also decreased antigenicity 100- to 200-fold. However, nucleotide monophosphates could be added with minimal changes in bioactivity. Longer prenyl pyrophosphates also retained bioactivity. Despite differences in CDR3 sequence, Vgamma2Vdelta2(+) clones and a transfectant responded similarly. Ag docking into a Vgamma2Vdelta2 TCR model reveals a potential binding site in germline regions of the Vgamma2Jgamma1.2 CDR3 and Vdelta2 CDR2 loops. Thus, Vgamma2Vdelta2(+) T cells recognize a core carbon chain and pyrophosphate moiety. This recognition is relatively unaffected by additions at distal positions to the core Ag unit.

Transfection

T-Lymphocyte Subsets - immunology

Diphosphates - metabolism

Polyisoprenyl Phosphates - chemistry

Organophosphorus Compounds - immunology

Diphosphates - chemical synthesis

Humans

Polyisoprenyl Phosphates - immunology

Epitopes, T-Lymphocyte - genetics

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

Organophosphorus Compounds - metabolism

Sesquiterpenes

Binding Sites - immunology

Diphosphates - immunology

Adult

Clone Cells

Epitopes, T-Lymphocyte - immunology

Cell Line

Jurkat Cells

Organophosphorus Compounds - chemistry

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

Antigens - metabolism

Polyisoprenyl Phosphates - metabolism

Antigens - chemistry

Diphosphates - chemistry

T-Lymphocyte Subsets - metabolism

Hemiterpenes

Antigens - immunology

Epitopes, T-Lymphocyte - metabolism

Antigens - genetics

Details

Title: Subtitle: Structural features of nonpeptide prenyl pyrophosphates that determine their antigenicity for human gamma delta T cells
Creators: Craig T Morita - Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa College of Medicine, Iowa City, IA 52242, USA. craig-morita@uiowa.edu
Hoi K Lee
Hong Wang
Hongmin Li
Roy A Mariuzza
Yoshimasa Tanaka
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.167(1), pp.36-41
DOI: 10.4049/jimmunol.167.1.36
PMID: 11418629
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Language: English
Date published: 07/01/2001
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094631802771

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