title: Specific CD8+ T cell responses correlate with control of simian immunodeficiency virus replication in Mauritian cynomolgus macaques.
abstract: Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8(+) T cells, but it is not clear whether particular CD8(+) T cell responses or a broad repertoire of epitope-specific CD8(+) T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: Melisa L
authors.initials: ML
authors.lastname: Budde
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Emily N
authors.initials: EN
authors.lastname: Chin
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ericsen
authors.forename: Matthew
authors.initials: M
authors.lastname: Scarlotta
authors.forename: Brian T
authors.initials: BT
authors.lastname: Cain
authors.forename: Ngoc H
authors.initials: NH
authors.lastname: Pham
authors.forename: Ericka A
authors.initials: EA
authors.lastname: Becker
authors.forename: Max
authors.initials: M
authors.lastname: Harris
authors.forename: Jason T
authors.initials: JT
authors.lastname: Weinfurter
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005805:Genes, MHC Class I; D014644:Genetic Variation; D006579:Heterozygote; D007371:Interferon-gamma / Q000276:immunology; D008252:Macaca fascicularis / Q000235:genetics / Q000821:virology; D008436:Mauritius; D017423:Sequence Analysis, RNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology*; D019562:Viral Load; D054334:Viral Regulatory and Accessory Proteins / Q000276:immunology; D014779:Virus Replication
chemical_list: C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins; D007371:Interferon-gamma