The high frequency Indian rhesus macaque MHC class I molecule, Mamu-B*01, does not appear to be involved in CD8+ T lymphocyte responses to SIVmac239

John T. Loffredo, John Sidney, Shari Piaskowski, Andrew Szymanski, Jessica Furlott, Richard Rudersdorf, Jason Reed, Bjoern Peters, Heather D. Hickman-Miller, Wilfried Bardet, William M. Rehrauer, David H. O'Connor, Nancy A. Wilson, William H. Hildebrand, Alessandro Sette, David I. Watkins

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Although the SIV-infected Indian rhesus macaque (Macaca mulatta) is the animal model most widely used for studying HIV infection, oar current understanding of the functional macaque MHC class I molecules is limited. To date, SIV-derived CD8+ T lymphocyte epitopes from only three high frequency macaque MHC class I molecules have been extensively characterized. In this study, we defined the peptide-binding properties of the high frequency Indian rhesus macaque class I molecule, Mamu-B*01 (∼26%). We first identified a preliminary binding motif by eluting and sequencing endogenously bound Mamu-B*01 ligands. We further characterized the peptide-bindieg characteristics using panels of single amino acid substitution analogs. Using this detailed motif, 507 peptides derived from SIVmac239 were identified and tested for their Mamu-B*01 binding capacity. Surprisingly, only 11 (2.2%) of these motif-containing peptides bound with IC50 values ≤500 nM. We assessed the immunogenicity of these peptides using freshly isolated PBMC from ten Mamu-B*01+ SIV-infected rhesus macaques in IFN-γ ELISPOT and IFN-γ/TNF-α intracellular cytokine staining assays. Lymphocytes from these SIV-infected macaques responded to none of these peptides. Furthermore, there was no sequence variation indicative of escape in the regions of the virus that encoded these peptides. Additionally, we could not confirm previous reports of SIV-derived Mamu-B*01-restricted epitopes in the Env and Gag proteins. Our results suggest that the high frequency MHC class I molecule, Mamu-B*01, is not involved in SIV-specific CD8+ T lymphocyte responses.

Original languageEnglish (US)
Pages (from-to)5986-5997
Number of pages12
JournalJournal of Immunology
Volume175
Issue number9
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Loffredo, J. T., Sidney, J., Piaskowski, S., Szymanski, A., Furlott, J., Rudersdorf, R., Reed, J., Peters, B., Hickman-Miller, H. D., Bardet, W., Rehrauer, W. M., O'Connor, D. H., Wilson, N. A., Hildebrand, W. H., Sette, A., & Watkins, D. I. (2005). The high frequency Indian rhesus macaque MHC class I molecule, Mamu-B*01, does not appear to be involved in CD8+ T lymphocyte responses to SIVmac239. Journal of Immunology, 175(9), 5986-5997. https://doi.org/10.4049/jimmunol.175.9.5986