Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B08 and HLA-B2705, bind peptides with sequence similarity1

• Published in: The Journal of immunology (1950) 2009-06, Vol.182 (12), p.7763-7775
• Main Authors: Loffredo, John T., Sidney, John, Bean, Alex T., Beal, Dominic R., Bardet, Wilfried, Wahl, Angela, Hawkins, Oriana E., Piaskowski, Shari, Wilson, Nancy A., Hildebrand, William H., Watkins, David I., Sette, Alessandro
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0900111

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, fifty percent of Mamu-B * 08 -positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic phase viremia below 1,000 vRNA 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 almost 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.