Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Bldg. 149, 13th Street, Charlestown, MA 02129, USA.
J Virol. 2011 Jun;85(12):5970-4. doi: 10.1128/JVI.00412-11. Epub 2011 Apr 6.
Epidemiological studies have shown the protective effect of KIR3DL1/HLA-Bw4 genotypes in human immunodeficiency virus type 1 (HIV-1) infection; however, the functional correlates for the protective effect remain unknown. We investigated whether human leukocyte antigen (HLA)-Bw4-presented HIV-1 peptides could affect the interaction between the inhibitory natural killer (NK) cell receptor KIR3DL1 and its ligand HLA-Bw4. Distinct HIV-1 epitopes differentially modulated the binding of KIR3DL1 to HLA-Bw4. Furthermore, cytotoxic T lymphocyte (CTL) escape mutations within the immunodominant HLA-B57 (Bw4)-restricted Gag epitope TSTLQEQIGW abrogated KIR3DL1 binding to HLA-B57, suggesting that sensing of CTL escape variants by NK cells can contribute to the protective effect of the KIR3DL1/HLA-Bw4 compound genotype.
流行病学研究表明，KIR3DL1/HLA-Bw4 基因型在人类免疫缺陷病毒 1（HIV-1）感染中具有保护作用；然而，其保护作用的功能相关性尚不清楚。我们研究了 HLA-Bw4 呈递的 HIV-1 肽是否会影响抑制性自然杀伤（NK）细胞受体 KIR3DL1 与其配体 HLA-Bw4 之间的相互作用。不同的 HIV-1 表位可调节 KIR3DL1 与 HLA-Bw4 的结合。此外，免疫优势 HLA-B57（Bw4）限制性 Gag 表位 TSTLQEQIGW 中的 CTL 逃逸突变破坏了 KIR3DL1 与 HLA-B57 的结合，提示 NK 细胞对 CTL 逃逸变异体的感知可能有助于 KIR3DL1/HLA-Bw4 复合基因型的保护作用。
