A15153G mAb, a novel tool for human TIGIT study

Abstract

Abstract T cell immunoglobulin and ITIM domain receptor (TIGIT) is a recently identified member of the PVR (poliovirus receptor) family of immunoglobulin-like domain containing proteins that is expressed on subsets of T cells and NK cells. With mouse model studies, TIGIT has been established as a new co-inhibitory, or “checkpoint” molecule in immune regulation. It is thus considered as a potential therapeutic target for cancer and for autoimmune/inflammatory disorders. However, due to limited availability of antibody reagents to human TIGIT, the biological function of this molecule in human cells, as well as its detailed mechanisms, has not been fully elucidated. We have developed a novel monoclonal antibody, clone A15153G, specific to human TIGIT. As expected, this antibody reacts with a subset of human peripheral blood T cells and most CD56+ NK cells. When A15153G antibody was applied in culture, it strongly suppressed anti-CD3 induced human T cell proliferation, suggesting that A15153G is an agonistic antibody. By multi-color flow cytometric analysis using this antibody, we found that the expression patterns of human TIGIT on the surface of CD4+ and CD8+ T cells are different. In the CD4+ T cells, TIGIT is mainly expressed in memory-like population; in contrast, significant percentage of “naïve” CD8+ T cells also expressed high levels of TIGIT in addition to memory population. Moreover, CD8+ T cells generally express higher levels TIGIT than CD4+ T cells. Studies of cytokine production profiles of TIGIT expressing cells are ongoing.