Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population.
KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.
López-Vázquez
A
A
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain. inmuno@hca.es
Miña-Blanco
A
A
Martínez-Borra
J
J
Njobvu
P D
PD
Suárez-Alvarez
B
B
Blanco-Gelaz
M A
MA
González
S
S
Rodrigo
L
L
López-Larrea
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology; D000328:Adult; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1 / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D015024:Zambia
D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1