Roti Michelle, Yang Junbao, Berger DeAnna, Huston Laurie, James Eddie A, Kwok William W
Benaroya Research Institute at Virginia Mason, University of Washington, Seattle, WA 98195, USA.
J Immunol. 2008 Feb 1;180(3):1758-68. doi: 10.4049/jimmunol.180.3.1758.
It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus. These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain. However, H5N1 hemagglutinin-reactive CD4(+) T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved. Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes. H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13. These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.
人们普遍认为，人类免疫系统对新出现的H5N1病毒缺乏免疫力。相比之下，大多数成年人通过接种疫苗或感染接触过甲型H1N1和H3N2流感病毒。1968年以前出生的成年人可能接触过H2N2病毒。我们推测，针对甲型H1N1、H3N2和H2N2流感病毒产生的CD4(+) T细胞也能识别H5N1表位。利用四聚体引导的表位图谱分析和抗原特异性II类四聚体来鉴定H5N1特异性T细胞表位并检测H5N1特异性T细胞反应。在检测的15名健康受试者中，有15名对甲型/越南/1203/2004（H5N1）病毒的基质蛋白、核蛋白和神经氨酸酶有强烈的CD4(+) T细胞反应。这些结果并不令人惊讶，因为甲型流感病毒的基质蛋白和核蛋白是保守的，而H5N1病毒的神经氨酸酶与正在传播的H1N1流感毒株的神经氨酸酶属于同一亚型。然而，在检测的14名受试者中，有14名也检测到了H5N1血凝素反应性CD4(+) T细胞，尽管血凝素的保守性较差。大多数细胞对H1、H2或H3血凝素表位具有交叉反应性。在体外也检测到了H5N1反应性T细胞，它们表现出记忆表型，并且能够分泌干扰素-γ、肿瘤坏死因子-α、白细胞介素-5和白细胞介素-13。这些数据表明健康的白种人受试者中存在H5N1交叉反应性T细胞，这意味着通过接种疫苗或感染接触甲型H1N1、H3N2或H2N2流感病毒可能会对H5N1病毒提供部分免疫力。
