研究発表を行った学会； Second Conference on Measuring Antigen-Specific Immune Responses
　　　２００６年６月１４日〜１７日 (Santorini, Greece)
タイトル； Different cytotoxic T lymphocyte activity and competitive antigen presentation toward two HIV-1 Nef epitopes, one of which is entirely contained within the other
発表者；本園　千尋　氏
　　　（熊本大学　エイズ学研究センター　ウイルス制御分野）
Abstract；
It is becoming evident that significant differences in the antiviral effectiveness of HIV-specific cytotoxic T lymphocytes (CTLs) among different specificities and restricting elements. But how effective HIV-specific CTL responses are induced remains unclear. Here, we characterized the CTL activity toward HLA-B35-restricted optimal epitopes derived from HIV-1 Nef, an immunodominant protein restricted by multiple HLA alleles. Among them, we focused on 11-mer and 8-mer epitope peptides, RPQVPLRPMTY (RY11) and VPLRPMTY (VY8), in which VY8 is contained within RY11. Analysis of PBMC of HIV-infected patients with HLA-B35 tetramers in complex with either peptides revealed that different fractions of CD8 T cells exclusively recognized one of two epitopes. Corroboratively, T cell receptor (TCR) analysis showed that the two epitopes were recognized by different sets of TCRs. Interestingly, in some patients, the VY8 epitope showed dominant responses while the RY11 epitope showed only weak responses; whereas RY11 showed dominant responses in the other patients vice versa. A number of CTL clones specific for either epitopes were established from PBMC samples of HIV-infected patients. All clones showed comparable cytolytic activity toward cells endogenously expressing Nef proteins. However, peptide-titration experiments showed VY8-specific CTL clones had >10 fold higher functional avidity toward the cognate peptide than RY11-specific ones, although the RY11 peptide bound HLA-B35 more potently than the VY8 peptide. Taken together, our data suggest that the inter-epitopic competition for antigen-processing and presentation have substantial effects on generating effective CTL responses against HIV infection.