期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 197, 期 9, 页码 1083-1091出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021752
关键词
PD-1 ligands; mutagenesis; costimulation; T cell activation
资金
- NCI NIH HHS [R01 CA097085, CA97085] Funding Source: Medline
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.
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