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.
Original language | English (US) |
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Pages (from-to) | 1083-1091 |
Number of pages | 9 |
Journal | Journal of Experimental Medicine |
Volume | 197 |
Issue number | 9 |
DOIs | |
State | Published - May 5 2003 |
Keywords
- Costimulation
- Mutagenesis
- PD-1 ligands
- T cell activation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology