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J. Virol. doi:10.1128/JVI.01816-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Major Histocompatibility Complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of SIV-infected rhesus macaque elite controllers

Department of Pathology and Laboratory Medicine and Wisconsin National Primate Research Center (WNPRC), University of Wisconsin-Madison, Madison, WI 53715; Laboratory of Genomic Diversity, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702; AIDS Vaccine Program/Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702

^* To whom correspondence should be addressed. Email: watkins{at}primate.wisc.edu.

	Abstract

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, MHC class 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 (vRNA) copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4+ T cell response. Here we describe five macaque MHC class II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003 and -DPB1*06) that restricted six SIV-specific CD4+ T cell epitopes in ECs and report the first association between specific MHC class II alleles and elite control. Interestingly, the macaque MHC class II alleles, -DRB1*1003 and -DRB1*0306, were enriched in this EC group (p= 0.02 and p= 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC class II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (p=<0.0001). The study of MHC class 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.

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