Moutaftsi Magdalini, Salek-Ardakani Shahram, Croft Michael, Peters Bjoern, Sidney John, Grey Howard, Sette Alessandro
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Eur J Immunol. 2009 Mar;39(3):717-22. doi: 10.1002/eji.200838815.
The recent identification of a large array of different vaccinia virus-derived CD8(+) T-cell epitopes offers a unique opportunity to systematically analyze the correlation between protective efficacy and variables such as kinetics of expression and function of viral proteins, binding affinity to MHC molecules, immunogenicity, and viral antigen processing/presentation. In the current study, 49 different H-2(b) restricted epitopes were tested for their ability to protect peptide-immunized C57Bl/6 mice from lethal i.n. challenge with vaccinia virus. The epitopes varied greatly in their ability to confer protection, ranging from complete protection with minimal disease to no protection at all. The function or kinetics of the viral antigen expression did not correlate with protective efficacy. However, binding affinity partially predicted protection efficacy and ultimately epitope immunogenicity and recognition of infected cells offered the best correlation.
最近发现了大量不同的源自痘苗病毒的CD8(+) T细胞表位,这为系统分析保护效力与多种变量之间的相关性提供了独特契机,这些变量包括病毒蛋白的表达动力学和功能、与MHC分子的结合亲和力、免疫原性以及病毒抗原加工/呈递等。在本研究中,测试了49种不同的H-2(b)限制性表位保护经肽免疫的C57Bl/6小鼠免受痘苗病毒致死性滴鼻攻击的能力。这些表位在赋予保护的能力上差异很大,从能提供最小疾病程度的完全保护到完全没有保护作用。病毒抗原表达的功能或动力学与保护效力无关。然而,结合亲和力部分预测了保护效力,最终表位免疫原性和对感染细胞的识别具有最佳相关性。