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- 39 South African clade-C-infected subjects were tested for IFN-γ responses to 5 OLP setsfrom clades A, B, D and matching consensus sets from clade C strains in China and South Africa. Responses to clade-C peptide sets did not differ in breadth and magnitude (intra-clade recognition), but were recognized significantly more than other clades' (inter-clade recognition). 13/19 C-clade recognized peptides were common between the peptide sets CDu422 from South Africa and CCH from China.
- Within Gag, a few highly conserved epitopes were found to be the regions where most inter-clade reactivity occurred i.e. 17/84 recognized peptides, were recognized from clades A, B, C, D by the C-infected subjects, and these peptides had lowest entropy. Peptides recognized that were from single clades however, had higher entropy scores. 7/17 peptides were in Gag p17 and 10/17 were in Gag p24.
- Computer predictions of epitope processing (proteasomal cleavage scores) and epitope presentation (MHC I binding scores) suggest that host immune selection pressure is responsible for the lack of peptide cross-recognition due to genetic divergence between clades.
- Peptide 32 (South Africa), SQNYPIVQNLQGQMV did not generate a CTL response in one subject whose autologous clade-C HIV-1 sequence was sqvSQNYPIVQNLQGQMV. EliSpot response to the subtype D variant of this peptide was elicited. Some other variants were not recognized since the varying residues were important for recognition. Chinese clade C and consensus clade B sequences were the same, therefore eliciting the same CTL response in clade C-carrying South African subjects.
Lycias Zembe, Wendy A. Burgers, Heather B. Jaspan, Linda-Gail Bekker, Helba Bredell, Gwynneth Stevens, Jill Gilmour, Josephine H. Cox, Patricia Fast, Peter Hayes, Eftyhia Vardas, Carolyn Williamson, and Clive M. Gray. Intra- and Inter-Clade Cross-Reactivity by HIV-1 Gag Specific T-Cells Reveals Exclusive and Commonly Targeted Regions: Implications for Current Vaccine Trials. PLoS One, 6(10):e26096, 2011. PubMed ID: 22022524.
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