Characterization of the peptide-binding specificity of Mamu-A*11 results in the identification of SIV-derived epitopes and interspecies cross-reactivity

Alessandro Sette, John Sidney, Huynh Hoa Bui, Marie France Del Guercio, Jeff Alexander, John Loffredo, David I. Watkins, Bianca R. Mothé

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The SIV-infected Indian rhesus macaque is the most established model of HIV infection, providing insight into pathogenesis and a system for testing novel vaccines. However, only a limited amount of information is available regarding the peptide-binding motifs and epitopes bound by their class I and class II MHC molecules. In this study, we utilized a library of over 1,000 different peptides and a high throughput MHC-peptide binding assay to detail the binding specificity of the rhesus macaque class I molecule Mamu-A*11. These studies defined the fine specificity of primary anchor positions, and dissected the role of secondary anchors, for peptides of 8-11 residues in length. This detailed information was utilized to develop size-specific polynomial algorithms to predict Mamu-A*11 binding capacity. Testing SIVmac239-derived Mamu-A* 11 binding peptides for recognition by peripheral blood mononuclear cells (PBMC) from Mamu-A*11-positive, SIV-infected macaques, identified five novel SIV-derived Mamu-A*11 epitopes. Finally, we detected extensive cross-reactivity at the binding level between Mamu-A*11 and the mouse H-2 class I molecule K k. Further experiments revealed that three out of four Mamu-A *11 binding peptides which bound Kk and were immunogenic in Kk mice were also recognized in Mamu-A*11-infected macaques. This is the first detailed description of mouse-macaque interspecies cross-reactivity, potentially useful in testing novel vaccines in mice and macaques.

Original languageEnglish (US)
Pages (from-to)53-68
Number of pages16
JournalImmunogenetics
Volume57
Issue number1-2
DOIs
StatePublished - Apr 1 2005

    Fingerprint

Keywords

  • AIDS
  • Epitope
  • Macaque
  • MHC
  • SIV

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this