Vdelta1 T cell receptor binds specifically to MHC I chain related A: molecular and biochemical evidences.
Human MHC class I chain-related A (MICA) is a tumor-associated antigen that can be recognized by Vdelta1 subset of tumor-infiltrating gammadelta T cells. We previously reported that immobilized recombinant MICA protein could induce the proliferation of tumor-infiltrating Vdelta1 gammadelta T cells in vitro. But there has been no direct evidence showing the engagement of gammadelta 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 gammadelta T cells. We expressed the coupled V domains from the MICA-induced T cells as a single polypeptide chain Vdelta Vgamma TCR (gammadelta scTCR). Such scTCR can specifically bind MICA of HeLa cells. Direct interaction of gammadelta scTCRs with in vitro expressed MICA was monitored using an IAsys biosensor. We found that the Vdelta1 scTCR can specifically bind to immobilized MICA molecule and MICA alpha1alpha2 domains are responsible for the binding reaction.
Zhao
Jianqing
J
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.
Huang
Jie
J
Chen
Hui
H
Cui
Lianxian
L
He
Wei
W
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins