title: The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3.
abstract: 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.
authors.affiliation: Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Murali
authors.initials: M
authors.lastname: Janakiram
authors.affiliation: Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Urvi A
authors.initials: UA
authors.lastname: Shah
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.affiliation: Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D060887:B7 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D007239:Infections / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016377:Organ Transplantation; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D060887:B7 Antigens; C423237:CD276 protein, human; D018106:CD28 Antigens; C400341:HHLA2 protein, human; D007136:Immunoglobulins; D011993:Recombinant Fusion Proteins; C585279:TMIGD2 protein, human; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
keywords: B7-H3; B7x; HHLA2; TMIGD2; immune checkpoint; immunotherapy