di Marzo Veronese F, Arnott D, Barnaba V, Loftus D J, Sakaguchi K, Thompson C B, Salemi S, Mastroianni C, Sette A, Shabanowitz J, Hunt D F, Appella E
Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Exp Med. 1996 Jun 1;183(6):2509-16. doi: 10.1084/jem.183.6.2509.
A subtractive analysis of peptides eluted from major histocompatibility complex (MHC) class I human histocompatibility leukocyte antigen (HLA)-A2.1 molecules purified from either human immunodeficiency virus type-1 (HIV-1)-infected or uninfected cells was performed using micro high-performance liquid chromatography and mass spectrometry. Three peptides unique to infected cells were identified and found to derive from a single protein, human vinculin, a structural protein not known to be involved in viral pathogenesis. Molecular and cytofluorometric analyses revealed vinculin mRNA and vinculin protein overexpression in B and T lymphocytes from HIV-1-infected individuals. Vinculin peptide-specific CTL activity was readily elicited from peripheral blood lymphocytes of the majority of HLA-A2.1+, HIV+ patients tested. Our observations suggest that atypical vinculin expression and MHC class I-mediated presentation of vinculin-derived peptides accompany HIV infection of lymphoid cells in vivo, with a resultant induction of antivinculin CTL in a significant portion of HIV+ (HLA-A2.1+) individuals.
利用微高效液相色谱法和质谱法，对从感染或未感染1型人类免疫缺陷病毒（HIV-1）的细胞中纯化得到的主要组织相容性复合体（MHC）I类人类组织相容性白细胞抗原（HLA）-A2.1分子洗脱的肽段进行了消减分析。鉴定出三个感染细胞特有的肽段，发现它们来自单一蛋白质——人类纽蛋白，一种未知参与病毒发病机制的结构蛋白。分子分析和细胞荧光分析显示，HIV-1感染个体的B淋巴细胞和T淋巴细胞中纽蛋白mRNA和纽蛋白蛋白表达上调。在大多数接受检测的HLA-A2.1+、HIV+患者的外周血淋巴细胞中，很容易诱导出针对纽蛋白肽段的细胞毒性T淋巴细胞（CTL）活性。我们的观察结果表明，在体内HIV感染淋巴细胞时，伴随有非典型的纽蛋白表达以及MHC I类介导的纽蛋白衍生肽段的呈递，从而在相当一部分HIV+（HLA-A2.1+）个体中诱导出抗纽蛋白CTL。
