TY - JOUR
T1 - Human leucocyte antigen supertypes and immune susceptibility to HIV-1, implications for vaccine design
AU - MacDonald, Kelly S.
AU - Matukas, Larissa
AU - Embree, Joanne E.
AU - Fowke, Keith
AU - Kimani, Joshua
AU - Nagelkerke, Nico J.D.
AU - Oyugi, Julius
AU - Kiama, Peter
AU - Kaul, Rupert
AU - Luscher, Mark A.
AU - Rowland-Jones, Sarah
AU - Ndinya-Achola, Jekoniah
AU - Ngugi, Elizabeth
AU - Bwayo, Job J.
AU - Plummer, Francis A.
N1 - Funding Information:
This work was supported by grants from the Canadian Institutes of Health Research (CIHR GR-13301), National Institutes of Health (AI34616), the Ontario HIV Treatment Network and the Ontario HIV Positive Action Fund. K.S.M. was the recipient of a Medical Research Council of Canada Research Fellowship and is a Career Scientist of the Ontario HIV Treatment Network. M.A.L. was supported by the Toronto Hospital Skate the Dream Fund and the Merrill Lynch HIV Fund, K.F. was the recipient of a National Health Research Development Program studentship. F.A.P. is a CIHR Senior Scientist. Study participants provided informed consent for their participation in this study. These studies were approved by the Ethical Review Boards of the Universities of Nairobi and Manitoba. Some of the data in this report has been published previously in part [35,36] .
PY - 2001/11/1
Y1 - 2001/11/1
N2 - 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.
AB - 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.
KW - AIDS/HIV
KW - Human leucocyte antigens supertypes
UR - https://www.scopus.com/pages/publications/0035500512
UR - https://www.scopus.com/pages/publications/0035500512#tab=citedBy
U2 - 10.1016/S0165-2478(01)00277-2
DO - 10.1016/S0165-2478(01)00277-2
M3 - Article
C2 - 11595302
AN - SCOPUS:0035500512
SN - 0165-2478
VL - 79
SP - 151
EP - 157
JO - Immunology Letters
JF - Immunology Letters
IS - 1-2
ER -