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
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands;
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.
J Immunol. 2017 Nov 15;199(10):3679-3690. doi: 10.4049/jimmunol.1700502. Epub 2017 Oct 11.
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-A205:01, and elucidated the binding capacity for virus-derived peptides. The macaque A205 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-B27 and Mamu-B008, molecules shown to be involved in elite control in human HIV type 1 and macaque SIV infections, respectively. In contrast, however, Mamu-A205 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-A205:01 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.
在不同的猕猴物种中，MHC基因大量存在，其基因产物的特征是细胞表面低表达以及肽结合裂隙高度保守。我们已对Mamu - A205:01的肽结合基序进行了表征，并阐明了其对病毒衍生肽的结合能力。猕猴A205同种异型在肽的第二位偏好碱性氨基酸精氨酸，在C末端偏好疏水和极性氨基酸。这些偏好与HLA - B27和Mamu - B008相同，这两种分子分别在人类1型HIV感染和猕猴SIV感染的精英控制中发挥作用。然而，相比之下，Mamu - A205优先结合8聚体肽。内质网滞留似乎是细胞表面表达较低 的原因。随后的肽结合研究表明，在感染SIV的恒河猴中，在Mamu - B008同种异型的背景下，Mamu - A2*05:01能够结合已知能引发强烈CD8 T细胞反应的SIV表位。因此，猕猴基因编码一种特殊的MHC I类分子，并且很可能只有在有合适的肽时才会转运到细胞表面。
