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.