title: Common HIV-1 peptide variants mediate differential binding of KIR3DL1 to HLA-Bw4 molecules.
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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Bldg. 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Lena
authors.initials: L
authors.lastname: Fadda
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Connor
authors.forename: Swati
authors.initials: S
authors.lastname: Kumar
authors.forename: Alicja
authors.initials: A
authors.lastname: Piechocka-Trocha
authors.forename: Clair M
authors.initials: CM
authors.lastname: Gardiner
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McVicar
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D016056:Immunodominant Epitopes; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding / Q000187:drug effects; D054341:Receptors, KIR3DL1 / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D016056:Immunodominant Epitopes; C515083:KIR3DL1 protein, human; D010455:Peptides; D054341:Receptors, KIR3DL1