van der Burg S H, Visseren M J, Brandt R M, Kast W M, Melief C J
Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
J Immunol. 1996 May 1;156(9):3308-14.
The impact of the MHC class I peptide binding stability on the immunogenicity of particular peptide Ags in class I-restricted cytotoxic T lymphocyte responses is not clearly established. Therefore, we have determined the dissociation rate of each peptide from MHC class I at 37 degrees C and compared this to that of a consensus CTL epitope. Newly defined immunogenic peptides formed relatively stable MHC-peptide complexes as shown by their low dissociation rates, whereas nonimmunogenic peptides displayed high dissociation rates. In addition virtually all previously described HLA-A*0201-restricted T cell epitopes showed low dissociation rates. Furthermore, we show that the immunogenicity of HIV-1-derived peptides can be predicted more accurately by their dissociation rate than by the MHC class I binding affinity. Selection of peptides based on affinity and their dissociation rate leads to a more precise identification of candidate CTL epitopes than selection based on affinity alone. These results help to understand why some peptides are recognized by CTL and, along with detailed knowledge of protein processing rules, therefore have important implications for the selection of peptides in peptide-based vaccines.
MHC I类分子肽结合稳定性对I类限制性细胞毒性T淋巴细胞反应中特定肽抗原免疫原性的影响尚未明确确立。因此，我们测定了每种肽在37℃时从MHC I类分子上的解离速率，并将其与共有CTL表位的解离速率进行比较。新定义的免疫原性肽形成相对稳定的MHC-肽复合物，表现为其解离速率较低，而非免疫原性肽则表现出高解离速率。此外，几乎所有先前描述的HLA-A*0201限制性T细胞表位均显示出低解离速率。而且，我们表明，基于解离速率比基于MHC I类分子结合亲和力能更准确地预测HIV-1衍生肽的免疫原性。基于亲和力及其解离速率选择肽比仅基于亲和力选择能更精确地鉴定候选CTL表位。这些结果有助于理解为何某些肽能被CTL识别，并且连同蛋白质加工规则的详细知识，因此对基于肽的疫苗中肽的选择具有重要意义。
