title: KIR-HLA-A and B alleles of the Bw4 epitope against HIV infection in discordant heterosexual couples in Chaco Argentina.
abstract: Activating and inhibitory killer immunoglobulin-like receptors (KIR) and their ligands HLA-Bw4 (loci A and B) were studied by way of establishing whether they can contribute to protection against HIV-1 infection in highly exposed and persistently seronegative (HESN) patients. Twenty-three HIV-1 serodiscordant heterosexual couples, 100 HIV-1(+) patients and 200 healthy individuals were included in this retrospective case-control study. HLA typing was performed by means of PCR followed by sequence-specific oligonucleotide probe reverse hybridization. KIR3DL1 and KIR3DS1 were studied by PCR sequence-specific primers. The frequency of KIR3DS1(3DS1/3DL1)-Bw4 combination was significantly higher in HESN patients versus the discordant couples (P = 0·0003) and HIV-1(+) patients (P = 0·0001). Conversely, the KIR3DL1/KIR3DL1 homozygosity was significantly decreased in HESN patients versus the discordant couples (P = 0·00003), and HIV-1(+) patients (P = 0·00066). The frequency of HLA-A*32 and HLA-B*44 was higher in HESN versus their discordant couples (P = 0·009; P = 0·049), and HIV-1(+) patients (P = 0·00002; P = 0·0001). This had greater significance in combination with KIR3DS1 (3DS1/3DL1). KIR3DS1(3DS1/3DL1) could have a greater effect on protection against HIV-1 infection in HESN patients when bound to a specific HLA allele, in this case HLA-A*32 and HLA-B*44, both Bw4 alleles. The differences probably arise both in the HLA alleles and in the subtypes of KIR receptors depending on the ethnic group studied.
authors.affiliation: Servicio de Genética Molecular e Histocompatibilidad, Hospital Julio C. Perrando, Resistencia, Chaco, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Habegger de Sorrentino
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sinchi
authors.forename: Karina
authors.initials: K
authors.lastname: Marinic
authors.forename: Rosana
authors.initials: R
authors.lastname: López
authors.forename: Ernesto
authors.initials: E
authors.lastname: Iliovich
mesh_terms: D000328:Adult; D000483:Alleles; D001118:Argentina; D000939:Epitopes; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D020010:Heterosexuality; D006801:Humans; D008297:Male; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D054340:Receptors, KIR
keywords: HIV-1; HLA, human leucocyte antigen; KIR3DL1; KIR3DS1; killer immunoglobulin-like receptor