Motif inference reveals optimal CTL epitopes presented by HLA class I alleles highly prevalent in southern Africa.
HIV-specific CTL play a central role in immune control of HIV. The basis for understanding the success or failure of this immune response requires identification of the specific epitopes targeted by CTL. However, in populations most severely affected by the global epidemic, this fundamental knowledge is hindered by the lack of characterization of many of the HLA class I alleles highly prevalent in such populations. Overall, the peptide-binding motif has been determined for a small minority (9%) of HLA class I alleles, with a strong bias toward those alleles prevalent in Caucasoid populations. These studies therefore set out to define, in a South African Zulu/Xhosa population at the epicenter of the epidemic, the epitopes presented by alleles highly prevalent, but for which the peptide-binding motif had not been characterized. Using a method of motif inference, epitopes presented by four such alleles prevalent in the Zulu/Xhosa population of Durban, South Africa, namely, B*3910, B*4201, B*8101, and Cw*1801, are described. Importantly, this approach may additionally facilitate optimization of epitopes in certain instances where conflicting reports in the literature exist regarding the peptide-binding motif, such as for HLA-A*2902, also highly prevalent in southern African populations. These data indicate that the previously anomalous position of HLA-A*2902 among HLA-A alleles, outside any recognized HLA-A supertype, is artifactual, and the true position of the A*2902 motif overlaps those of the A1 and A24 supertypes.
Honeyborne
Isobella
I
Department of Paediatrics, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom.
Rathod
Almas
A
Buchli
Rico
R
Ramduth
Dhanwanthie
D
Moodley
Eshia
E
Rathnavalu
Prinisha
P
Chetty
Senica
S
Day
Cheryl
C
Brander
Christian
C
Hildebrand
William
W
Walker
Bruce D
BD
Kiepiela
Photini
P
Goulder
Philip J R
PJ
D000353:Africa, Southern; D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001665:Binding Sites / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005805:Genes, MHC Class I; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015488:HIV Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D010455:Peptides