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

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

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • B7 Antigens / genetics
  • B7 Antigens / immunology
  • B7 Antigens / metabolism
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • Graft Rejection / prevention & control*
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Immunoglobulins / metabolism
  • Immunomodulation
  • Immunotherapy / methods*
  • Infections / immunology
  • Infections / therapy*
  • Lymphocyte Activation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Organ Transplantation
  • Recombinant Fusion Proteins / therapeutic use*
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / genetics
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / immunology
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / metabolism

Substances

  • Antibodies, Monoclonal
  • B7 Antigens
  • CD276 protein, human
  • CD28 Antigens
  • HHLA2 protein, human
  • Immunoglobulins
  • Recombinant Fusion Proteins
  • TMIGD2 protein, human
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human