title: T cell response specificity and magnitude against SIVmac239 are not concordant in major histocompatibility complex-matched animals.
abstract: BACKGROUND
  CD8+ T cell responses, restricted by major histocompatibility complex (MHC) class I molecules, are critical to controlling human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) replication. Previous studies have used MHC-matched siblings and monozygotic twins to evaluate genetic and stochastic influences on HIV-specific T cell responses and viral evolution. Here we used a genetically restricted population of Mauritian cynomolgus macaques (MCM) to characterize T cell responses within nine pairs of MHC-matched animals.
  
  
  RESULTS
  In MHC-matched animals, there was considerable heterogeneity in the specificity and magnitude of T cell responses detected via individual peptide gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. These findings were further supported by full proteome pooled peptide matrix ELISPOT data collected from this cohort at 52 weeks post-infection. Interestingly, peptide regions that elicited dominant T cell responses were more commonly shared between MHC-matched MCM than peptide regions that elicited non-dominant T cell responses.
  
  
  CONCLUSIONS
  Our findings suggest that, while some T cell responses mounted during chronic infection by MHC-matched MCM are similar, the majority of responses are highly variable. Shared responses detected in this study between MHC-matched MCM were directed against epitopes that had previously elicited relatively dominant responses in MCM with the same MHC class I haplotype, suggesting that the factors that influence dominance may influence the reproducibility of responses as well. This may be an important consideration for future T cell-based vaccines aiming to consistently and reproducibly elicit protective T cell responses.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Cain
authors.forename: Ngoc H
authors.initials: NH
authors.lastname: Pham
authors.forename: Melisa L
authors.initials: ML
authors.lastname: Budde
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Jason T
authors.initials: JT
authors.lastname: Weinfurter
authors.forename: Matthew
authors.initials: M
authors.lastname: Scarlotta
authors.forename: Max
authors.initials: M
authors.lastname: Harris
authors.forename: Emily
authors.initials: E
authors.lastname: Chin
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA. doconnor@primate.wisc.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D007371:Interferon-gamma / Q000378:metabolism; D008251:Macaca; D008285:Major Histocompatibility Complex / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D007371:Interferon-gamma