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J Exp Med. 2003 May 5;197(9):1083-91. Epub 2003 Apr 28.

Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction.

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  • 1Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

B7-H1 and B7-DC are ligands for PD-1, a receptor implicated in negative regulation of T and B cell functions. These ligands, however, also costimulate T cell responses. It remains elusive whether or not costimulation is mediated through PD-1. By comparative molecular modeling and site-directed mutagenesis, we found that nonconserved residues between these ligands on the A'GFCC'C" face mediate interaction with PD-1. This indicates significant structural heterogeneity of the interactions between PD-1 and its ligands. Importantly, ligand mutants with abolished PD-1 binding capacity could still costimulate proliferation and cytokine production of T cells from normal and PD-1-deficient mice. Our results reveal unique binding characteristics of B7-H1 and B7-DC and provide direct evidence for an independent costimulatory receptor other than PD-1.

PMID:
12719480
[PubMed - indexed for MEDLINE]
PMCID:
PMC2193977
Free PMC Article
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