A Specialist Macaque MHC Class I Molecule with HLA-B27-like Peptide-Binding Characteristics

• Published in: The Journal of immunology (1950) 2017-11, Vol.199 (10), p.3679-3690
• Main Authors: de Groot, Natasja G, Heijmans, Corrine M C, de Ru, Arnoud H, Janssen, George M C, Drijfhout, Jan W, Otting, Nel, Vangenot, Christelle, Doxiadis, Gaby G M, Koning, Frits, van Veelen, Peter A, Bontrop, Ronald E
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Antigen Presentation; Arginine; CD8 antigen; Cell Line; Cell surface; Endoplasmic reticulum; Epitopes; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - metabolism; Genetic Predisposition to Disease; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; HIV - physiology; HIV Antigens - metabolism; HIV Infections - genetics; HIV Infections - immunology; HLA-B27 Antigen - genetics; Humans; Hydrophobicity; Immunity, Cellular; Lymphocytes T; Macaca; Major histocompatibility complex; Peptides; Peptides - metabolism; Protein Binding; Simian Acquired Immunodeficiency Syndrome - genetics; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Immunodeficiency Virus - physiology; T-Lymphocytes, Cytotoxic - immunology; Viral Load; Virus Replication; Viruses
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700502

In different macaque species, the MHC gene is present in abundance, and its gene products are characterized by low cell-surface expression and a highly conserved peptide-binding cleft. We have characterized the peptide-binding motif of Mamu-A2*05:01, and elucidated the binding capacity for virus-derived peptides. The macaque A2*05 allotype prefers the basic amino acid arginine at the second position of the peptide, and hydrophobic and polar amino acids at the C-terminal end. These preferences are shared with HLA-B*27 and Mamu-B*008, molecules shown to be involved in elite control in human HIV type 1 and macaque SIV infections, respectively. In contrast, however, Mamu-A2*05 preferentially binds 8-mer peptides. Retention in the endoplasmic reticulum seems to be the cause of the lower cell-surface expression. Subsequent peptide-binding studies have illustrated that Mamu-A2*05:01 is able to bind SIV-epitopes known to evoke a strong CD8 T cell response in the context of the Mamu-B*008 allotype in SIV-infected rhesus macaques. Thus, the macaque gene encodes a specialized MHC class I molecule, and is most likely transported to the cell surface only when suitable peptides become available.