Department of Clinical Medicine, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
PLoS One. 2011;6(8):e22680. doi: 10.1371/journal.pone.0022680. Epub 2011 Aug 3.
Cytotoxic T Lymphocytes (CTLs) play a central role in controlling HIV-replication. Although numerous CTL epitopes have been described, most are in subtype B or C infection. Little is known about CTL responses in CRF01_AE infection. Gag CTL responses were investigated in a cohort of 137 treatment-naïve HIV-1 infected Thai patients with high CD4+ T cell counts, using gIFN Enzyme-Linked Immunospot (ELISpot) assays with 15-mer overlapping peptides (OLPs) derived from locally dominant CRF01_AE Gag sequences. 44 OLPs were recognized in 112 (81.8%) individuals. Both the breadth and magnitude of the CTL response, particularly against the p24 region, positively correlated with CD4+ T cell count and inversely correlated with HIV viral load. The breadth of OLP response was also associated with slower progression to antiretroviral therapy initiation. Statistical analysis and single peptide ELISpot assay identified at least 17 significant associations between reactive OLP and HLA in 12 OLP regions; 6 OLP-HLA associations (35.3%) were not compatible with previously reported CTL epitopes, suggesting that these contained new CTL Gag epitopes. A substantial proportion of CTL epitopes in CRF01_AE infection differ from subtype B or C. However, the pattern of protective CTL responses is similar; Gag CTL responses, particularly against p24, control viral replication and slow clinical progression.
细胞毒性 T 淋巴细胞（CTLs）在控制 HIV 复制中发挥核心作用。尽管已经描述了许多 CTL 表位，但大多数存在于亚型 B 或 C 感染中。关于 CRF01_AE 感染中的 CTL 反应知之甚少。在一项由 137 名未经治疗的 HIV-1 感染泰国患者组成的队列中，使用源自当地主导的 CRF01_AE Gag 序列的 15 聚体重叠肽（OLP）进行 gIFN 酶联免疫斑点（ELISpot）测定，研究了 gag CTL 反应。在 112 名（81.8%）个体中鉴定出 44 个 OLP。CTL 反应的广度和强度，特别是针对 p24 区域，与 CD4+T 细胞计数呈正相关，与 HIV 病毒载量呈负相关。OLP 反应的广度也与更早开始抗逆转录病毒治疗的进展相关。统计分析和单肽 ELISpot 分析在 12 个 OLP 区域中鉴定出至少 17 个反应性 OLP 与 HLA 之间的显著关联；在 6 个 OLP-HLA 关联（35.3%）与先前报道的 CTL 表位不兼容，表明这些表位包含新的 CTL Gag 表位。CRF01_AE 感染中的 CTL 表位很大一部分与亚型 B 或 C 不同。然而，保护性 CTL 反应的模式是相似的；Gag CTL 反应，特别是针对 p24 的反应，控制病毒复制并减缓临床进展。
