アクティブボード・2015年12月
・・・・・2015年12月 2日更新・・・・・
研究発表を行った学会;
・第44回日本免疫学会学術集会
2015年11月18日〜20日(札幌市)
タイトル;Nef mediated immune evasion activities of HLA class II-restricted antigen presentation.
発表者;Macdonald Mahiti 氏
(熊本大学 エイズ学研究センター 上野プロジェクト研究室)
要旨;
HLA class II (HLA-II)-restricted CD4+ T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. However, HIV-1 Nef circumvents this immune response by manipulating HLA-II antigen presentation pathway through down-regulation of HLA-DR and up-regulation of invariant chain (Ii) from the surface of cells. However, these Nef activities during acute/early infection remain uncharacterized. Here, we isolated Nef clones from plasma viral RNA of 47 and 46 HIV-1-infected patients at acute/early and chronic phase of infection, respectively. The ability of these Nef clones to up-regulate Ii, down-regulate HLA-DR and down-regulate HLA class I from virus-infected cell surface were simultaneously analyzed by flow cytometry. HLA-I down-regulation function was relatively conserved among acute/early Nef clones, whereas both HLA-DR down-regulation functions displayed broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at the acute/early infection stage, suggesting these avtivities are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our study reveals enhanced Nef's ability to evade HLA class II-restricted immune responses during acute/early infection, hjghlighting impotance of these Nef functions towards disease progression early after HIV-1 transmission.