Unidad de Procesamiento Antigénico, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Immunol Cell Biol. 2011 May;89(4):558-65. doi: 10.1038/icb.2010.125. Epub 2010 Oct 26.
Short viral antigens bound to human major histocompatibility complex (HLA) class I molecules are presented on infected cells. Vaccine development frequently relies on synthetic peptides to identify optimal HLA class I ligands. However, when natural peptides are analyzed, more complex mixtures are found. By immunoproteomics analysis, we identify in this study a physiologically processed HLA ligand derived from the human respiratory syncytial virus matrix protein that is very different from what was expected from studies with synthetic peptides. This natural HLA-Cw4 class I ligand uses alternative interactions to the anchor motifs previously described for its presenting HLA-Cw4 class I molecule. Finally, this octameric peptide shares its C-terminal core with the H-2D(b) nonamer ligand previously identified in the mouse model. These data have implications for the identification of antiviral cytotoxic T lymphocyte responses and for vaccine development.
短的病毒抗原与人类主要组织相容性复合体 (HLA) Ⅰ类分子结合，在受感染的细胞上呈现。疫苗的开发经常依赖于合成肽来识别最佳的 HLA Ⅰ类配体。然而，当分析天然肽时，会发现更复杂的混合物。通过免疫蛋白质组学分析，我们在这项研究中鉴定出一种源自人类呼吸道合胞病毒基质蛋白的生理加工的 HLA 配体，与使用合成肽进行的研究非常不同。这种天然的 HLA-Cw4 Ⅰ类配体使用与以前为其呈递 HLA-Cw4 Ⅰ类分子描述的锚定基序不同的替代相互作用。最后，这个八聚体肽与以前在小鼠模型中鉴定的 H-2D(b) 九聚体配体共享其 C 末端核心。这些数据对识别抗病毒细胞毒性 T 淋巴细胞反应和疫苗开发具有重要意义。
