Journal article
Vγ2Vδ2 T Cell Receptor Recognition of Prenyl Pyrophosphates is Dependent on all Complementarity Determining Regions1
The Journal of immunology (1950), Vol.184(11), pp.6209-6222
06/01/2010
DOI: 10.4049/jimmunol.1000231
PMCID: PMC3069129
PMID: 20483784
Abstract
γδ T cells differ from αβ T cells in the antigens they recognize and their functions in immunity. While most αβ T cell receptors (TCR) recognize peptides presented by MHC class I or II, human γδ T cells expressing Vγ2Vδ2 TCRs recognize nonpeptide prenyl pyrophosphates. To define the molecular basis for this recognition, the effect of mutations in the TCR complementarity-determining regions (CDR) was assessed. Mutations in all CDR loops altered recognition and cover a large footprint. Unlike murine γδ TCR recognition of the MHC class Ib T22 protein, there was no CDR3δ motif required for recognition because only 1 residue is required. Instead, the length and sequence of CDR3γ was key. Although a potential prenyl pyrophosphate-binding site was defined by Lys109 in Jγ1.2 and Arg51 in CDR2δ, the area outlined by critical mutations is much larger. These results show that prenyl pyrophosphate recognition is primarily by germline-encoded regions of the γδ TCR, allowing a high proportion of Vγ2Vδ2 TCRs to respond. This underscores its parallels to innate immune receptors. Our results also provide strong evidence for the existence of an antigen-presenting molecule for prenyl pyrophosphates.
This is an author-produced version of a manuscript accepted for publication in
The Journal of Immunology
(
The JI
). The American Association of Immunologists, Inc. (AAI), publisher of
The JI
, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by
The JI;
hence, it may differ from the final version published in
The JI
(online and in print). AAI (
The JI
) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at
www.jimmunol.org
.
Details
- Title: Subtitle
- Vγ2Vδ2 T Cell Receptor Recognition of Prenyl Pyrophosphates is Dependent on all Complementarity Determining Regions1
- Creators
- Hong Wang - Division of Immunology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242 USAZhimei Fang - Division of Immunology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242 USACraig T Morita - Division of Immunology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.184(11), pp.6209-6222
- DOI
- 10.4049/jimmunol.1000231
- PMID
- 20483784
- PMCID
- PMC3069129
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 06/01/2010
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094598002771
Metrics
26 Record Views