Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses

Immunity. 2007 Jul;27(1):111-22. doi: 10.1016/j.immuni.2007.05.016. Epub 2007 Jul 12.

Abstract

Pathways in the B7:CD28 family of costimulatory molecules regulate T cell activation and tolerance. B7-dependent responses in Cd28(-/-)Ctla4(-/-) T cells together with reports of stimulatory and inhibitory functions for Programmed Death-1 Ligand 1 or 2 molecules (PD-L1 or PD-L2) have suggested additional receptors for these B7 family members. We show that B7-1 and PD-L1 interacted with affinity intermediate to that of B7-1:CD28 and B7-1:CTLA-4. The PD-L1:B7-1 interface overlapped with the B7-1:CTLA-4 and PD-L1:PD-1 (Programmed Death-1) interfaces. T cell activation and cytokine production were inhibited by the interaction of B7-1 with PD-L1. The responses of PD-1-deficient versus PD-1,B7-1 double-deficient T cells to PD-L1 and of CD28,CTLA-4 double-deficient versus CD28,CTLA-4,PD-L1 triple-deficient T cells to B7-1 demonstrated that PD-L1 and B7-1 interact specifically to inhibit T cell activation. Our findings point to a substantial bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism*
  • B7-1 Antigen / physiology
  • B7-H1 Antigen
  • COS Cells
  • Cell Line
  • Cell Proliferation
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Humans
  • Ligands
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptides / deficiency
  • Peptides / metabolism*
  • Peptides / physiology
  • Protein Binding / genetics
  • Protein Binding / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • B7-1 Antigen
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Cytokines
  • Ligands
  • Membrane Glycoproteins
  • Peptides