title: The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.
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, 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-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-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr., Madison, WI 53711, USA.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Giraldo-Vela
authors.forename: Richard
authors.initials: R
authors.lastname: Rudersdorf
authors.forename: Chungwon
authors.initials: C
authors.lastname: Chung
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Lyle T
authors.initials: LT
authors.lastname: Wallace
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bimber
authors.forename: Gretta J
authors.initials: GJ
authors.lastname: Borchardt
authors.forename: Debra L
authors.initials: DL
authors.lastname: Fisk
authors.forename: Chrystal E
authors.initials: CE
authors.lastname: Glidden
authors.forename: John T
authors.initials: JT
authors.lastname: Loffredo
authors.forename: Shari M
authors.initials: SM
authors.lastname: Piaskowski
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Furlott
authors.forename: Juan P
authors.initials: JP
authors.lastname: Morales-Martinez
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: William M
authors.initials: WM
authors.lastname: Rehrauer
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D019562:Viral Load
chemical_list: D006684:HLA-DR Antigens; D012367:RNA, Viral