Immobilized MICA could expand human Vδ1 γδ T cells in vitro that displayed major histocompatibility complex class I chain-related a-dependent cytotoxicity to human epithelial carcinomas

Abstract

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 Vδ1 subset of γδ 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 γδ T cells of the Vδ1 phenotype in vitro. These Vδ1 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 Vδ1 γδ T cells, whereas MICA-reactive Vδ1 γδ T cells might serve as a new candidate for adoptive cellular therapy of tumours.