The B7-CD28 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 [CD276], B7x [B7-H4/B7S1], and HHLA2 [B7H7/B7-H5]/TMIGD2 [IGPR-1/CD28H]) 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, HHLA2, and TMIGD2 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.
Bibliographical noteFunding Information:
MJ is supported by AMC grant UM1CA121947. Research in the Zang lab is supported by NIH R01CA175495 and R01DK100525, DOD Established Investigator Idea Development Award PC131008, Pfizer CTI, Hengrui Medicine Co., and Irma T. Hirschl/Monique Weill-Caulier Trust (to X. Zang).
- immune checkpoint