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PMID: 17629517 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Immunity ·Vol. 27 ·No. 1 ·2007-07-00 ·Pages 111-22

Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ

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.

MeSH Terms
Animals B7-1 Antigen/genetics,metabolism,physiology B7-H1 Antigen COS Cells Cell Line Cell Proliferation Cells, Cultured Chlorocebus aethiops Cytokines/antagonists & inhibitors,biosynthesis Down-Regulation/genetics,immunology Humans Ligands Membrane Glycoproteins/deficiency,metabolism,physiology Mice Mice, Inbred C57BL Mice, Knockout Peptides/deficiency,metabolism,physiology Protein Binding/genetics,immunology T-Lymphocytes/cytology,immunology,metabolism
Chemicals
B7-1 Antigen B7-H1 Antigen Cd274 protein, mouse Cytokines Ligands Membrane Glycoproteins Peptides
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Butte Manish J
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Keir Mary E
Phamduy Theresa B
Sharpe Arlene H
Freeman Gordon J
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.05.016
Published
2007-07-00
Epub
2007-00-12
Pages
111-22
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2707944
Subset
IM
Grants
NIAID NIH HHS · R01 AI040614-05 · United States
NIAID NIH HHS · P01 AI056299-05 · United States
NIAID NIH HHS · P01 AI056299 · United States
NIAID NIH HHS · R01 AI040614-06 · United States
NIAID NIH HHS · P01 AI056299-04 · United States
NIAID NIH HHS · R37 AI038310 · United States
NIAID NIH HHS · R01 AI038310-06 · United States
NCRR NIH HHS · S10RR017948-01A1 · United States
NIAID NIH HHS · R01 AI040614 · United States
NIAID NIH HHS · R01 AI038310-07 · United States
NIAID NIH HHS · R01 AI38310 · United States
NCRR NIH HHS · S10 RR017948 · United States
NIAID NIH HHS · R01 AI038310 · United States
NIAID NIH HHS · P01 AI56299 · United States
NIAID NIH HHS · R01 AI038310-05 · United States
NIAID NIH HHS · R01 AI46414 · United States
NIAID NIH HHS · R01 AI040614-07 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2007.05.016 PMC Full Text View journal details
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