研究発表を行った学会； AIDS vaccine 2005
2005年　9月　6日〜 9日（カナダ　モントリオール）
タイトル； ANALYSIS OF TWO IMMUNODOMINANT POL EPITOPES PRESENTED BY HLA-A*51 ASSOCIATED WITH SLOW PROGRESSION TO AIDS: SPECULATION OF MECHANISMS FOR SUPRESSION OF VIRAL REPLICATION IN HLA-B*5101-POSITIVE LTNP
発表者；川島　夕佳　氏
　　　（熊本大学　エイズ学研究センター　ウイルス制御分野）
Abstract；
HLA-B57, -B27 and -B51 are well known to be associated with slow progression to AIDS. However, it is still unclear why HIV-1-infected individuals carrying these alleles show slow progression to AIDS. We recently reported that HLA-B*5101-restricted CTLs specific for two Pol epitopes (Pol743-9 and Pol283-8) effectively killed HIV-1-infected CD4+ T cells and suppressed HIV-1 replication although Nef-mediated HLA-class I down-regulation were found in HIV-1-infected target cells. Analysis of these epitope-specific CD8+ T cells using by tetramer and epitope mutations in HIV-1-infected hemophiliacs are expected to clarify the mechanisms of effective suppression of HIV-1 replication in long-term non-progressor (LTNP).
We analyzed HLA-B*5101-restricted CTLs specific for two Pol and one Gag epitopes and sequences of these epitopes in 7 HLA-B*5101+hemophiliacs (3 LTNPs and 4 slow progressors) without ART therapy. In addition, the epitope sequences were analyzed in 5 HLA-B*5101+progressors. Two Pol-epitope-specific CTLs were found in 3 LTNPs and one slow progressor with low viral load, while only Pol283-specific CD8+ T cells were found in 3 slow progressors with moderate and high viral load. No mutation on Pol283-8 was found in LTNP, whereas mutations at position 8 were detected in all slow progressors. These mutations were also found in 5 progressors. These results imply that the mutations at position 8 of Pol283-8 affect Pol283-specific T cell recognition. On the other hand, mutations at position 1 or 5 of Pol743-9 were detected in 2 of 4 slow progressors and in 3 of 5 progressors, implying the different mechanisms of HIV-1 from specific CD8+ T cells in HIV-1-infected HLA-B*5101+ individuals.
The present study suggests that induction of these Pol-specific CD8+ T cells and epitope stability are important factors for suppression of HIV-1 replication in HLA-B*5101+LTNP. A strategy to induce CD8+ T cells specific for epitopes such as Pol743-9 and Pol283-8 is expected for HIV-1 vaccine development.