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Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity.

Abstract
HLA-B27- and -B57-positive HIV-infected humans have long been associated with control of HIV replication, implying that CD8(+) T cell responses contribute to control of viral replication. In a similar fashion, 50% of Mamu-B*08-positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic-phase viremia <1000 viral RNA copies/ml. Interestingly, Mamu-B*08-restricted SIV-derived epitopes appeared to match the peptide binding profile for HLA-B*2705 in humans. We therefore defined a detailed peptide-binding motif for Mamu-B*08 and investigated binding similarities between the macaque and human MHC class I molecules. Analysis of a panel of approximately 900 peptides revealed that despite substantial sequence differences between Mamu-B*08 and HLA-B*2705, the peptide-binding repertoires of these two MHC class I molecules share a remarkable degree of overlap. Detailed knowledge of the Mamu-B*08 peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8(+) T cell immune responses directed against epitopes in Gag, Vpr, and Env. All 13 Mamu-B*08-restricted epitopes contain an R at the position 2 primary anchor and 10 also possess either R or K at the N terminus. Such dibasic peptides are less prone to cellular degradation. This work highlights the relevance of the Mamu-B*08-positive SIV-infected Indian rhesus macaque as a model to examine elite control of immunodeficiency virus replication. The remarkable similarity of the peptide-binding motifs and repertoires for Mamu-B*08 and HLA-B*2705 suggests that the nature of the peptide bound by the MHC class I molecule may play an important role in control of immunodeficiency virus replication.
AuthorsJohn T Loffredo, John Sidney, Alex T Bean, Dominic R Beal, Wilfried Bardet, Angela Wahl, Oriana E Hawkins, Shari Piaskowski, Nancy A Wilson, William H Hildebrand, David I Watkins, Alessandro Sette
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 12 Pg. 7763-75 (Jun 15 2009) ISSN: 1550-6606 [Electronic] United States
PMID19494300 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Ligands
  • Peptide Library
  • Peptides
  • bacteriophage T7 induced DNA polymerase
  • DNA-Directed DNA Polymerase
Topics
  • Amino Acid Sequence
  • Animals
  • DNA-Directed DNA Polymerase
  • Epitopes, T-Lymphocyte (chemistry, immunology)
  • Histocompatibility Antigens Class I (chemistry, immunology)
  • Humans
  • Ligands
  • Macaca mulatta
  • Molecular Sequence Data
  • Peptide Library
  • Peptides (immunology, metabolism)
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Simian Immunodeficiency Virus (immunology)
  • Virus Replication

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