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Immunol Rev. 2017 Mar;276(1):26-39. doi: 10.1111/imr.12521.

The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3.

Author information

1
Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
2
Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
3
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
4
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
5
Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
6
Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.

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.

KEYWORDS:

B7-H3; B7x; HHLA2; TMIGD2; immune checkpoint; immunotherapy

PMID:
28258693
PMCID:
PMC5338461
DOI:
10.1111/imr.12521
[Indexed for MEDLINE]
Free PMC Article

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