T cell response specificity and magnitude against SIVmac239 are not concordant in major histocompatibility complex-matched animals

Retrovirology

David H O’Connor²  Thomas C Friedrich³  Shelby L O’Connor²  Emily Chin⁴  Max Harris¹  Matthew Scarlotta¹  Jason T Weinfurter²  Justin M Greene¹  Melisa L Budde²  Ngoc H Pham¹  Brian T Cain¹ 

[1] Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA;Wisconsin National Primate Research Center, Madison, Wisconsin, USA;Department of Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin, USA;Department of Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin, USA

关键词: Reproducibility;    T cell;    ELISPOT;    MCM;    SIVmac239;   

Others  :  806925
DOI  :  10.1186/1742-4690-10-116

 received in 2013-06-21, accepted in 2013-10-10,  发布年份 2013

【 摘 要 】

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.

Findings

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.

【 授权许可】

   
2013 Cain et al.; licensee BioMed Central Ltd.

【 图 表 】

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