The third group of the B7‐ CD CD 28 immune checkpoint family: HHLA HHLA 2, TMIGD TMIGD 2, B7x, and B7‐H3

摘要

Summary The B7‐ CD 28 family of ligands and receptors play important roles in T‐cell co‐stimulation and co‐inhibition. Phylogenetically they can be divided into three groups. The recent discovery of the new molecules (B7‐H3 [ CD 276], B7x [B7‐H4/B7S1], and HHLA 2 [B7H7/B7‐H5]/ TMIGD 2 [ IGPR ‐1/ CD 28H]) of the group III has expanded therapeutic possibilities for the treatment of human diseases. In this review, we describe the discovery, structure, and function of B7‐H3, B7x, HHLA 2, and TMIGD 2 in immune regulation. We also discuss their roles in important pathological states such as cancers, autoimmune diseases, transplantation, and infection. Various immunotherapeutical approaches are emerging including antagonistic monoclonal antibodies and agonistic fusion proteins to inhibit or potentiate these molecules and pathways in cancers and autoimmune diseases.