Human leucocyte antigen supertypes and immune susceptibility to HIV-1, implications for vaccine design.
T cell responses against HIV-1 have been identified in a number of exposed uninfected populations. We hypothesized that the ability to mount an effective T cell response is partly determined by the human leucocyte antigens (HLA) phenotype of the individual. We examined whether certain HLA supertypes were associated with differential HIV-1 susceptibility in sexually exposed adults and in the setting of mother to child HIV-1 transmission. By multivariate analysis, decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related class I HLA alleles (A2/6802 supertype) in sexually exposed adults (Hazard ratio=0.42, 95% confidence intervals (CI): 0.22-0.81, P=0.009) and perinatally exposed infants (Odds ratio=0.12, 95% CI: 0.03-0.54, P=0.006). The alleles in this HLA supertype are known in some cases, to present the same peptide epitopes (termed 'supertopes'), for T cell recognition. The identification of HIV-1 supertopes, which are associated with protection from HIV-1 infection, has important implications for the application of epitope-based HIV-l vaccines in a variety of racial groups.
MacDonald
K S
KS
Department of Microbiology, Mount Sinai Hospital, Room 1484, 600 University Avenue, Toronto, Ont., M5G 1X5 Canada. kmacdonald@mtsinai.on.ca
Matukas
L
L
Embree
J E
JE
Fowke
K
K
Kimani
J
J
Nagelkerke
N J
NJ
Oyugi
J
J
Kiama
P
P
Kaul
R
R
Luscher
M A
MA
Rowland-Jones
S
S
Ndinya-Achola
J
J
Ngugi
E
E
Bwayo
J J
JJ
Plummer
F A
FA
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007630:Kenya; D015999:Multivariate Analysis; D011247:Pregnancy; D012307:Risk Factors; D011477:Sex Work; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines; D006680:HLA Antigens