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 Watkins

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

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Macaca mulatta
T-Lymphocytes
Peptides
Macaca
env Gene Products
gag Gene Products
Enzyme-Linked Immunospot Assay
T-Lymphocyte Epitopes
Amino Acid Substitution
Inhibitory Concentration 50
HIV Infections
Epitopes
Animal Models
Lymphocytes
Staining and Labeling
Cytokines
Ligands
Viruses

ASJC Scopus subject areas

  • Immunology

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

In: Journal of Immunology, Vol. 175, No. 9, 01.11.2005, p. 5986-5997.

Research output: Contribution to journalArticle

Loffredo, JT, Sidney, J, Piaskowski, S, Szymanski, A, Furlott, J, Rudersdorf, R, Reed, J, Peters, B, Hickman-Miller, HD, Bardet, W, Rehrauer, WM, O'Connor, DH, Wilson, NA, Hildebrand, WH, Sette, A & Watkins, D 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, vol. 175, no. 9, pp. 5986-5997.
Loffredo JT, Sidney J, Piaskowski S, Szymanski A, Furlott J, Rudersdorf R et al. 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. 2005 Nov 1;175(9):5986-5997.
Loffredo, John T. ; Sidney, John ; Piaskowski, Shari ; Szymanski, Andrew ; Furlott, Jessica ; Rudersdorf, Richard ; Reed, Jason ; Peters, Bjoern ; Hickman-Miller, Heather D. ; Bardet, Wilfried ; Rehrauer, William M. ; O'Connor, David H. ; Wilson, Nancy A. ; Hildebrand, William H. ; Sette, Alessandro ; Watkins, David. / 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. In: Journal of Immunology. 2005 ; Vol. 175, No. 9. pp. 5986-5997.
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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.",
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AU - Loffredo, John T.

AU - Sidney, John

AU - Piaskowski, Shari

AU - Szymanski, Andrew

AU - Furlott, Jessica

AU - Rudersdorf, Richard

AU - Reed, Jason

AU - Peters, Bjoern

AU - Hickman-Miller, Heather D.

AU - Bardet, Wilfried

AU - Rehrauer, William M.

AU - O'Connor, David H.

AU - Wilson, Nancy A.

AU - Hildebrand, William H.

AU - Sette, Alessandro

AU - Watkins, David

PY - 2005/11/1

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N2 - 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.

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