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.
Although the SIV-infected Indian rhesus macaque (Macaca mulatta) is the animal model most widely used for studying HIV infection, our 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 ( approximately 26%). We first identified a preliminary binding motif by eluting and sequencing endogenously bound Mamu-B*01 ligands. We further characterized the peptide-binding characteristics using panels of single amino acid substitution analogs. Using this detailed motif, 507 peptides derived from SIV(mac)239 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 < or =500 nM. We assessed the immunogenicity of these peptides using freshly isolated PBMC from ten Mamu-B*01+ SIV-infected rhesus macaques in IFN-gamma ELISPOT and IFN-gamma/TNF-alpha 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.
Loffredo
John T
JT
Wisconsin National Primate Research Center (WNPRC), University of Wisconsin, Madison, WI 53715, USA.
Sidney
John
J
Piaskowski
Shari
S
Szymanski
Andrew
A
Furlott
Jessica
J
Rudersdorf
Richard
R
Reed
Jason
J
Peters
Bjoern
B
Hickman-Miller
Heather D
HD
Bardet
Wilfried
W
Rehrauer
William M
WM
O'Connor
David H
DH
Wilson
Nancy A
NA
Hildebrand
William H
WH
Sette
Alessandro
A
Watkins
David I
DI
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C092249:Mamu-B 01 antigen, Macaca mulatta; D010446:Peptide Fragments; D014764:Viral Proteins; D007371:Interferon-gamma