Giraldo-Vela Juan P, Rudersdorf Richard, Chung Chungwon, Qi Ying, Wallace Lyle T, Bimber Benjamin, Borchardt Gretta J, Fisk Debra L, Glidden Chrystal E, Loffredo John T, Piaskowski Shari M, Furlott Jessica R, Morales-Martinez Juan P, Wilson Nancy A, Rehrauer William M, Lifson Jeffrey D, Carrington Mary, Watkins David I
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr., Madison, WI 53711, USA.
J Virol. 2008 Jan;82(2):859-70. doi: 10.1128/JVI.01816-07. Epub 2007 Nov 7.
The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRBw606, -DRBw2104, -DRB10306, -DRB11003, and -DPB106) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB11003 and -DRB10306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B17-positive animals that did not express Mamu-DRB11003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.
CD4(+) T细胞在控制人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）复制中的作用尚未完全明确。尽管在控制病毒复制的个体中已检测到强烈的HIV和SIV特异性CD4(+) T细胞反应，但主要组织相容性复合体II类（MHC-II）分子与疾病缓慢进展之间尚未建立明确联系。在一组196只感染SIVmac239的印度恒河猴中，有一群猴子将病毒复制控制在每毫升低于1000个病毒RNA拷贝。这些精英控制者（ECs）产生了广泛的SIV特异性CD4(+) T细胞反应。在此，我们描述了五个猕猴MHC-II等位基因（Mamu-DRBw606、-DRBw2104、-DRB10306、-DRB11003和-DPB106），它们在ECs中限制了六个SIV特异性CD4(+) T细胞表位，并报告了特定MHC-II等位基因与精英控制之间的首次关联。有趣的是，猕猴MHC-II等位基因Mamu-DRB11003和-DRB10306在这个EC组中富集（P值分别为0.02和0.05）。此外，同时表达这两个MHC-II等位基因的Mamu-B17阳性SIV感染恒河猴的病毒载量显著低于未表达Mamu-DRB11003和-DRB10306的Mamu-B*17阳性动物（P值<0.0001）。对控制病毒复制的猕猴中MHC-II等位基因的研究可能会增进我们对CD4(+) T细胞在抑制HIV/SIV复制中的作用的理解，并进一步加深我们对HIV疫苗设计的理解。
