Characterization of the peptide-binding specificity of Mamu-A*11 results in the identification of SIV-derived epitopes and interspecies cross-reactivity.
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 Kk. 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.
Sette
Alessandro
A
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Sidney
John
J
Bui
Huynh-Hoa
HH
del Guercio
Marie-France
MF
Alexander
Jeff
J
Loffredo
John
J
Watkins
David I
DI
Mothé
Bianca R
BR
D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007371:Interferon-gamma / Q000032:analysis; D008253:Macaca mulatta; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity
D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D007371:Interferon-gamma