A Specialist Macaque MHC Class I Molecule with HLA-B*27-like Peptide-Binding Characteristics

作者：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

来源：The Journal of Immunology, 2017, 199(10): 3679-3690.

DOI：10.4049/jimmunol.1700502

In different macaque species, the MHC A2*05 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 MamuA2*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 A2*05 gene encodes a specialized MHC class I molecule, and is most likely transported to the cell surface only when suitable peptides become available.

• 出版日期2017-11-15