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

A Specialist Macaque MHC Class I Molecule with HLA-B*27-like Peptide-Binding Characteristics.
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de Groot NG, Heijmans CMC, de Ru AH, Janssen GMC, Drijfhout JW, Otting N, Vangenot C, Doxiadis GGM, Koning F, van Veelen PA, Bontrop RE,


de Groot NG, Heijmans CMC, de Ru AH, Janssen GMC, Drijfhout JW, Otting N, Vangenot C, Doxiadis GGM, Koning F, van Veelen PA, Bontrop RE, (click to view)

de Groot NG, Heijmans CMC, de Ru AH, Janssen GMC, Drijfhout JW, Otting N, Vangenot C, Doxiadis GGM, Koning F, van Veelen PA, Bontrop RE,

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Journal of immunology (Baltimore, Md. : 1950) 2017 10 11() pii 10.4049/jimmunol.1700502

Abstract

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 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 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.

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