Vδ1 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 Vδ1 subset of tumor-infiltrating γδ T cells. We previously reported that immobilized recombinant MICA protein could induce the proliferation of tumor-infiltrating Vδ1 γδ T cells in vitro. But there has been no direct evidence showing the engagement of γδ 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 γδ T cells. We expressed the coupled V domains from the MICA-induced T cells as a single polypeptide chain VδVγ TCR (γδ scTCR). Such scTCR can specifically bind MICA of HeLa cells. Direct interaction of γδ scTCRs with in vitro expressed MICA was monitored using an IAsys biosensor. We found that the Vδ1 scTCR can specifically bind to immobilized MICA molecule and MICAα1α2 domains are responsible for the binding reaction.