Immobilized MICA could expand human Vdelta1 gammadelta T cells in vitro that displayed major histocompatibility complex class I chain-related A-dependent cytotoxicity to human epithelial carcinomas.
Human major histocompatibility complex class I chain-related A (MICA) is a human leucocyte antigen-related polymorphic molecule, which is expressed on many kinds of epithelial tumours and can be recognized by the Vdelta1 subset of gammadelta T cells. In the present study, monoclonal antibodies (MoAbs) were produced in mice immunized with recombinant MICA (rMICA)*008. It was found that MICA was expressed on ovarian and colonic tumour tissues and could be detected by these anti-MICA MoAbs. The immobilized rMICA could induce the proliferation of human ovarian epithelial carcinoma- or colonic carcinoma-derived gammadelta T cells of the Vdelta1 phenotype in vitro. These Vdelta1 T cells displayed a strong, broad-range cytolytic activity towards tumour cell lines positive for MICA. The efficiency of this cytolytic activity depended greatly on the level of MICA expressed on the cell surface and could be inhibited by anti-MICA MoAbs. Therefore, MICA may play an important role in immune responses against epithelial tumours and function as a stimulating factor for the growth of Vdelta1 gammadelta T cells, whereas MICA-reactive Vdelta1 gammadelta T cells might serve as a new candidate for adoptive cellular therapy of tumours.
Qi
J
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, PR China.
Zhang
J
J
Zhang
S
S
Cui
L
L
He
W
W
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D002277:Carcinoma / Q000276:immunology*; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D012334:RNA, Neoplasm; D016692:Receptors, Antigen, T-Cell, gamma-delta