HIV-1附属蛋白特异性细胞毒性T细胞应答研究  

Specific Cytotoxic T Lymphocytes Responses to Human Immunodeficiency Virus Type 1 Accessory Proteins

作　　者：黄德东[1] 孙永涛[1] 翟嵩[1] 赵曙光[1] 王少扬[1] 庄严[1] 李新红[1] 康文臻[1] 余旭 Marcus Altfeld Bruce D.Walker 

机构地区：[1]第四军医大学唐都医院全军感染病诊疗中心 [2]Partners AIDS Research Center,Massachusetts General Hospital,Harvard Medical School,Boston,MA02129,USA

出　　处：《中国病毒学》2006年第6期529-535,共7页Virologica Sinica

基　　金：国际合作基金(NIAIDContractNO.N01-AI-30024)

摘　　要：人类免疫缺陷病毒(Humanimmunodeficiencyvirus,HIV)附属蛋白Nef、Vpu、Vpr和Vif在病毒复制中起着关键作用,并能被细胞毒性T细胞(CytotoxicTLymphocyte,CTL)识别。然而,对我国HIV感染者体内附属蛋白特异性的CTL应答研究比较少。本研究应用覆盖HIV-1B、C亚型附属蛋白(Nef、Vpu、Vpr和Vif)的142个肽段作为抗原,通过酶联免疫斑点实验(Enzyme-LinkedImmunospot,ELISPOT)检测61例中国HIV/AIDS患者和10例HIV-1血清阴性对照的HIV-1附属蛋白特异性CTL应答。无论对HIV-1B亚型还是HIV-1C亚型附属蛋白都能产生特异性CTL应答,特别是Nef区蛋白的反应频率和累积应答强度都较高(P<0.001),B、C亚型间的应答频率和累积应答强度都无显著差别(P>0.05),其免疫优势区也大致相同。附属蛋白特异性的累积CTL应答强度将近达到总应答的21%。这些结果表明尽管HIV-1附属蛋白的体积小,但它们在诱导特异性的CTL应答中发挥了重要作用,对评价HIV-1免疫应答的幅度和特异性以及研发针对中国人群的HIV疫苗有重要的意义。The HIV-1 accessory proteins （ Nef, Vpu,Vpr and Vif ） are essential for viral replication, and may be processed for recognition by CTL However, only limited data are available to evaluate the CTL responses against these proteins in naturally infected individuals. In this study, CTL responses against the accessory proteins of HIV-1 clade B（HIV-1B） and C （HIV-1C） were analyzed in 61 HIV-1 infected individuals and 10 HIV-1 negative controls by using 142 overlapping peptides according to the consensus sequence spanning the entire accessory proteins. Peptide-specific interferon-7（IFN-7） production was measured by Enzyme-Linked Immunospot （ELISPOT） assay. Either HIV-1B or HIV-1C accessory proteins serve as targets for HIV-1-specific CTL, especially the peptides in Nef region are targeted at higher cumulative magnitude and wider frequency than other accessory proteins（P〈0.001）. The cumulative magnitude and the frequency of CTL responses between clade B and C are not significantly different （P〉0.05）, including the immunodominant domains. The cumulative magnitude of HIV-1-specific CD8^＋T-cell responses to accessory proteins of HIV-1B or HIV-1C contribute nearly 21% of the total HIV-1-specific CTL response. These data indicate that, despite the sizes of these accessory proteins targeted by CTL in natural HIV-1 infection is very small, these proteins contribute considerably to the total HIV-1-specific CD8^＋ T-cell responses. These findings are relevant for the evaluation of the specificity and breadth of immune responses in naturally infected individuals, and will be useful for the design and testing of candidate HIV- 1 vaccines.

关 键 词：人类免疫缺陷病毒1型 细胞毒性T细胞 酶联免疫斑点实验 

分 类 号：R392[医药卫生—免疫学]