Rhesus macaque MHC class I molecules present HLA-B-like peptides.
SIV-infected Indian rhesus macaques (Macaca mulatta) are an important animal model for humans infected with HIV. Understanding macaque (M. mulatta class I (Mamu)) MHC class I-peptide binding facilitates the comparison of SIV- and HIV-specific cellular immune responses. In this study, we characterized the endogenous peptide-binding properties of three Mamu-A (A*02, A*08, A*11) and three Mamu-B (B*01, B*03, B*12) class I molecules. Motif comparisons revealed that five of the six macaque class I molecules (A*02, A*08, A*11, B*01, and B*03) have peptide-binding motifs similar to those of human class I molecules. Of the 65 macaque endogenous peptide ligands that we sequenced by tandem mass spectroscopy, 5 were previously eluted from HLA class I molecules. Nonamers predominated among the individual ligands, and both the motifs and the individual ligands indicated P2, P9, and various ancillary anchors. Interestingly, peptide binding of the Mamu-A and Mamu-B molecules exhibited cross-species peptide-presentation overlap primarily with HLA-B molecules. Indeed, all of the macaque class I molecules appeared HLA-B-like in peptide presentation. Remarkably, the overlap in macaque- and HLA-peptide presentation occurred despite divergent class I peptide-binding grooves. Macaque and human class I differing by up to 42 aa (13-23%) within the alpha-1 and alpha-2 domains, including substantial divergence within specificity pockets A-F, bound the same endogenous peptide. Therefore, endogenous peptide characterization indicates that macaque class I molecules may be the functional equivalents of HLA-B molecules.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Heather D
HD
Hickman-Miller
Wilfried
W
Bardet
Angela
A
Gilb
Angela D
AD
Luis
Kenneth W
KW
Jackson
David I
DI
Watkins
William H
WH
Hildebrand
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D006678:HIV / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013045:Species Specificity
D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C089390:Mamu-A 02 antigen; C092249:Mamu-B 01 antigen, Macaca mulatta; D011994:Recombinant Proteins; D004247:DNA