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Title: V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences

Abstract

Human MHC class I chain-related A (MICA) is a tumor-associated antigen that can be recognized by V{delta}1 subset of tumor-infiltrating {gamma}{delta} T cells. We previously reported that immobilized recombinant MICA protein could induce the proliferation of tumor-infiltrating V{delta}1 {gamma}{delta} T cells in vitro. But there has been no direct evidence showing the engagement of {gamma}{delta} T cell receptors (TCR) of the induced cells with MICA. In the current investigation, we show that MICA induces specific cytolytic activity of the expanded {gamma}{delta} T cells. We expressed the coupled V domains from the MICA-induced T cells as a single polypeptide chain V{delta}V{gamma} TCR ({gamma}{delta} scTCR). Such scTCR can specifically bind MICA of HeLa cells. Direct interaction of {gamma}{delta} scTCRs with in vitro expressed MICA was monitored using an IAsys biosensor. We found that the V{delta}1 scTCR can specifically bind to immobilized MICA molecule and MICA{alpha}1{alpha}2 domains are responsible for the binding reaction.

Authors:
 [1];  [1];  [1];  [1];  [2]
  1. Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 (China)
  2. Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 (China). E-mail: heweiimu@public.bta.net.cn
Publication Date:
OSTI Identifier:
20795857
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 339; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2005.10.198; PII: S0006-291X(05)02465-4; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; CELL PROLIFERATION; HELA CELLS; IN VITRO; MICA; NEOPLASMS; POLYPEPTIDES; RECEPTORS; TOXICITY

Citation Formats

Zhao Jianqing, Huang Jie, Chen Hui, Cui Lianxian, and He Wei. V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences. United States: N. p., 2006. Web. doi:10.1016/J.BBRC.2005.1.
Zhao Jianqing, Huang Jie, Chen Hui, Cui Lianxian, & He Wei. V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences. United States. doi:10.1016/J.BBRC.2005.1.
Zhao Jianqing, Huang Jie, Chen Hui, Cui Lianxian, and He Wei. Fri . "V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences". United States. doi:10.1016/J.BBRC.2005.1.
@article{osti_20795857,
title = {V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences},
author = {Zhao Jianqing and Huang Jie and Chen Hui and Cui Lianxian and He Wei},
abstractNote = {Human MHC class I chain-related A (MICA) is a tumor-associated antigen that can be recognized by V{delta}1 subset of tumor-infiltrating {gamma}{delta} T cells. We previously reported that immobilized recombinant MICA protein could induce the proliferation of tumor-infiltrating V{delta}1 {gamma}{delta} T cells in vitro. But there has been no direct evidence showing the engagement of {gamma}{delta} T cell receptors (TCR) of the induced cells with MICA. In the current investigation, we show that MICA induces specific cytolytic activity of the expanded {gamma}{delta} T cells. We expressed the coupled V domains from the MICA-induced T cells as a single polypeptide chain V{delta}V{gamma} TCR ({gamma}{delta} scTCR). Such scTCR can specifically bind MICA of HeLa cells. Direct interaction of {gamma}{delta} scTCRs with in vitro expressed MICA was monitored using an IAsys biosensor. We found that the V{delta}1 scTCR can specifically bind to immobilized MICA molecule and MICA{alpha}1{alpha}2 domains are responsible for the binding reaction.},
doi = {10.1016/J.BBRC.2005.1},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 339,
place = {United States},
year = {Fri Jan 06 00:00:00 EST 2006},
month = {Fri Jan 06 00:00:00 EST 2006}
}
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  • {gamma}{delta} T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human {gamma}{delta} T cells of the V{sub {delta}}1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V{sub {delta}}1 {gamma}{delta} T-cell receptor (TCR) showed expected overall structural homology to antibodies, {alpha}{beta}, and other {gamma}{delta} TCRs, but complementary determining region conformations and conservation of V{sub {delta}}1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves asmore » a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on {gamma}{delta} T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of {gamma}{delta} T-cell/target cell interfaces.« less