Common HIV-1 Peptide Variants Mediate Differential Binding of KIR3DL1 to HLA-Bw4 Molecules

Authors

• Lena Fadda, Harvard University
• Geraldine M. O'Connor, National Cancer Institute—Frederick
• Swati Kumar, Harvard University
• Alicja Piechocka-Trocha, Harvard University
• Clair M. Gardiner, Trinity College
• Mary Carrington, National Institutes of HealthFollow
• Daniel W. McVicar, National Cancer Institute—Frederick
• Marcus Altfeld, Harvard University

Date of this Version

2011

Comments

Published in JOURNAL OF VIROLOGY, June 2011, 85:12, p. 5970–5974; doi:10.1128/JVI.00412-11

Abstract

Epidemiological studies have shown the protective effect of KIR3DL1/HLA-Bw4 genotypes in human immunodeficiency virus type 1 (HIV-1) infection; however, the functional correlates for the protective effect remain unknown. We investigated whether human leukocyte antigen (HLA)-Bw4-presented HIV-1 peptides could affect the interaction between the inhibitory natural killer (NK) cell receptor KIR3DL1 and its ligand HLA-Bw4. Distinct HIV-1 epitopes differentially modulated the binding of KIR3DL1 to HLA-Bw4. Furthermore, cytotoxic T lymphocyte (CTL) escape mutations within the immunodominant HLA-B57 (Bw4)-restricted Gag epitope TSTLQEQIGW abrogated KIR3DL1 binding to HLA-B57, suggesting that sensing of CTL escape variants by NK cells can contribute to the protective effect of the KIR3DL1/HLA-Bw4 compound genotype.