研究発表を行った学会； AIDS VACCINE 2005 INTERNATIONAL CONFERENCE
　　　　２００５年　９月　６日〜　９日（ Montreal, Quebec, Canada ）
タイトル； EFFECT OF TWO HLA-A*1101-RESTRICTED NEF-SPECIFIC CTLS ON HIV-1 EVOLUTION
発表者；小泉　寛和　氏
　　　（熊本大学　エイズ学研究センター　ウイルス制御分野）
Abstract；
A previous study using the cohort of Northern Thailand indicated that HLA-A*1101 may play an important role in protection of HIV-1 infection, and that HLA-A*1101-restricted Nef73-specific CTLs were frequently induced in highly exposed to HIV-1 but remain persistently seronegative HLA-A*1101+ individuals. We previously showed that HLA-A*1101-restricted Nef84 epitope-specific CTLs were frequently induced in HLA-A*1101+ HIV-1 infected individuals. These findings imply that Nef73- specific or Nef84-specific CTLs can suppress HIV-1 replication and provide a strong immune pressure in HIV-1-infected individuals. This immune pressure may produce the escape mutants from Nef73- or Nef84-specific CTLs. We therefore investigated these escape mutants in HLA-A*1101+ HIV-1-infected individuals.
We analyzed the region containing Nef73 (QVPLRPMTYK) and Nef84 (AVDLSHFLK) HIV-1 epitopes from both 6 HLA-A*1101-positive HIV-1 clade B-infected and 7 HLA-A*1101-negative HIV-1 clade B- or clade E- infected individuals who have not been treated with anti retrovirus therapy. There was no significant difference in Nef73 epitope sequence between HLA-A*1101-positive and -negative individuals. The sequence from most of these patients was wild type of Nef73. On the other hand, 6 out of 6 HLA-A*1101-positive individuals had V-to-L amino acid substitution at the second position and K-to-R amino acid substitution at the ninth position of Nef84 (Nef84-2L9R). In contrast, HLA-A*1101-negative individuals had wild type, Nef84-2L, Nef84-2F (clade E) or Nef84-2F6F (clade E). Analysis of HLA-A*1101-restricted Nef84-specific CTL clone for cells pulsed with these peptides revealed that the CTL clone recognized Nef84 and Nef84-2L more than Nef84-2L9R. These results suggested that HIV-1 Nef84-2L9R mutant was selected by Nef84-specific immune-pressure. The present study suggested that Nef84-specific CTLs can more effectively suppress HIV-1 replication than Nef73-specific CTLs and that they influence HIV-1 evolution. Vaccine development for HIV-1 carrying Nef84-2L9R is required in Asian countries where HLA-A11 is frequently found.