Immunogenetics

, Volume 65, Issue 5, pp 371–386

Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles

Authors

    • Department of Vaccine DiscoveryLa Jolla Institute for Allergy and Immunology
    • Department of Biological SciencesCalifornia State University San Marcos
  • Scott Southwood
    • Department of Vaccine DiscoveryLa Jolla Institute for Allergy and Immunology
  • John Sidney
    • Department of Vaccine DiscoveryLa Jolla Institute for Allergy and Immunology
  • A. Michelle English
    • Department of ChemistryUniversity of Virginia
  • Amanda Wriston
    • Department of ChemistryUniversity of Virginia
  • Ilka Hoof
    • Center for Biological Sequence Analysis, Department of Systems BiologyTechnical University of Denmark
    • The Bioinformatics Centre, Department of Biology and The Biotech Research and Innovation CentreCopenhagen University
  • Jeffrey Shabanowitz
    • Department of ChemistryUniversity of Virginia
  • Donald F. Hunt
    • Department of ChemistryUniversity of Virginia
  • Alessandro Sette
    • Department of Vaccine DiscoveryLa Jolla Institute for Allergy and Immunology
Original Paper

DOI: 10.1007/s00251-013-0686-9

Cite this article as:
Mothé, B.R., Southwood, S., Sidney, J. et al. Immunogenetics (2013) 65: 371. doi:10.1007/s00251-013-0686-9

Abstract

Chinese rhesus macaques are of particular interest in simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) research as these animals have prolonged kinetics of disease progression to acquired immunodeficiency syndrome (AIDS), compared to their Indian counterparts, suggesting that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of major histocompatibility complex (MHC) molecules, including their MHC/peptide-binding motifs, provides valuable information for measuring cellular immune responses and deciphering outcomes of infection and vaccine efficacy. In this study, we have provided detailed characterization of six prevalent Chinese rhesus macaque MHC class I alleles, yielding a combined phenotypic frequency of 29 %. The peptide-binding specificity of two of these alleles, Mamu-A2*01:02 and Mamu-B*010:01, as well as the previously characterized allele Mamu-B*003:01 (and Indian rhesus Mamu-B*003:01), was found to be analogous to that of alleles in the HLA-B27 supertype family. Specific alleles in the HLA-B27 supertype family, including HLA-B*27:05, have been associated with long-term nonprogression to AIDS in humans. All six alleles characterized in the present study were found to have specificities analogous to HLA supertype alleles. These data contribute to the concept that Chinese rhesus macaque MHC immunogenetics is more similar to HLA than their Indian rhesus macaque counterparts and thereby warrants further studies to decipher the role of these alleles in the context of SIV infection.

Keywords

MHC Nonhuman primate Chinese rhesus macaques MHC/peptide-binding motif

Supplementary material

251_2013_686_MOESM1_ESM.pdf (60 kb)
ESM 1 Development of MHC:peptide-binding assays: identification of high affinity radiolabeled ligands in direct binding assays. Various peptide ligands were used as radiolabel probes in direct binding MHC dose titration experiments to ascertain binding potential to purified MHC class I molecules. The optimal radiolabeled identified for each assay was: SHSHVGYTL for Mamu-A2*01:02, RAEDNADYL for Mamu-A7*01:03, YFAIAENESK for Mamu-B*066:01, MSAPPAEYK for Mamu-B*090:01, SDIDGDRYV for Mamu-B*087:01, and SHIDRVYTL for Mamu-B*010:01. Peptides identified as high affinity radiolabeled ligands for various other assays were utilized as negative controls (as indicated) to demonstrate assay specificity. (PDF 60 kb)
251_2013_686_MOESM2_ESM.pdf (56 kb)
ESM 2 (PDF 56 kb)
251_2013_686_MOESM3_ESM.pdf (65 kb)
ESM 3 (PDF 65 kb)
251_2013_686_MOESM4_ESM.pdf (2 mb)
ESM 4 (PDF 2073 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013