Wentworth P A, Vitiello A, Sidney J, Keogh E, Chesnut R W, Grey H, Sette A
Cytel Corporation, San Diego, CA 92121, USA.
Eur J Immunol. 1996 Jan;26(1):97-101. doi: 10.1002/eji.1830260115.
HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity with human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA-A2.1/Kb transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the level of overlap between the A2.1-restricted CTL repertoire of A2.1/Kb-transgenic mice and A2.1+ humans. In both humans and mice, a major histocompatibility complex affinity threshold of approximately 500 nM appears to determine the capacity of a peptide to elicit a CTL response. Good concordance between the human data in vitro and mouse data in vivo was observed with 85% of the high-binding peptides, 58% of the intermediate binders, and 83% of the low/negative binders. Although some peptides immunogenic for mouse CTL but not for humans (and vice versa) could be identified, the data as a whole suggest an extensive overlap between T cell receptor repertoires of mouse and human CTL and support the use of HLA-transgenic mice for the identification of potential human CTL epitopes.
在体外细胞毒性T淋巴细胞（CTL）诱导实验中，用人外周血单个核细胞对HLA - A2.1结合肽（n = 38）进行免疫原性筛选，并在体内免疫后用HLA - A2.1/Kb转基因小鼠的脾细胞进行筛选。对这些数据进行汇总和分析，以确定A2.1/Kb转基因小鼠和A2.1 +人类的A2.1限制性CTL库之间的重叠程度。在人类和小鼠中，约500 nM的主要组织相容性复合体亲和力阈值似乎决定了肽引发CTL反应的能力。在高结合肽中，85%、中等结合肽中58%以及低/阴性结合肽中83%的体外人类数据和体内小鼠数据之间观察到良好的一致性。虽然可以鉴定出一些对小鼠CTL有免疫原性但对人类没有免疫原性的肽（反之亦然），但总体数据表明小鼠和人类CTL的T细胞受体库之间存在广泛重叠，并支持使用HLA转基因小鼠来鉴定潜在的人类CTL表位。
