title: An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1.
abstract: Mutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed the appearance of a mutation within the B*57-restricted TW10 epitope (G9E) that did not facilitate strong escape from T cell recognition. The NK cell receptor KIR3DL1, carried by these patients, is known to recognize HLA-B*5703 and is associated with good control of HIV-1. Therefore, we tested whether the G9E mutation influenced the binding of HLA-B*5703 to soluble KIR3DL1 protein by surface plasmon resonance, and while the wild-type sequence and a second (T3N) variant were recognized, the G9E variant abrogated KIR3DL1 binding. We extended the study to determine the peptide sensitivity of KIR3DL1 interaction with epitopes carrying mutations near the C termini of TW10 and a second HLA-B*57-restricted epitope, IW9. Several amino acid changes interfered with KIR3DL1 binding, the most extreme of which included the G9E mutation commonly selected by HLA-B*57. Our results imply that during HIV-1 infection, some early-emerging variants could affect KIR-HLA interaction, with possible implications for immune recognition.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Brackenridge
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Evans
authors.forename: Mireille
authors.initials: M
authors.lastname: Toebes
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
authors.forename: Michael K P
authors.initials: MK
authors.lastname: Liu
authors.forename: Kati
authors.initials: K
authors.lastname: di Gleria
authors.forename: Ton N
authors.initials: TN
authors.lastname: Schumacher
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Davis
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Gillespie
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015235:HLA-B Antigens; D006801:Humans; D057131:Immune Evasion; D020125:Mutation, Missense; D011485:Protein Binding; D054341:Receptors, KIR3DL1 / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D054341:Receptors, KIR3DL1