title: MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques.
abstract: The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)-infected major histocompatibility complex (MHC)-homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Lhost
authors.forename: Ericka A
authors.initials: EA
authors.lastname: Becker
authors.forename: Ann M
authors.initials: AM
authors.lastname: Detmer
authors.forename: Randall C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Macnair
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: Julie A
authors.initials: JA
authors.lastname: Karl
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bimber
authors.forename: Simon M
authors.initials: SM
authors.lastname: Lank
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Tuscher
authors.forename: Edward T
authors.initials: ET
authors.lastname: Mee
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Rose
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D008252:Macaca fascicularis / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008436:Mauritius; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D014766:Viremia / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000821:virology