Selection and identification of HLA-A2-restricted CTL epitopes within heparanase / 中华微生物学和免疫学杂志

ABSTRACT

Objective To select and identify human leukocyte antigen(HLA)-A2-restricted T-cell epitope within heparanase(Hpa),and to provide aeademic bases for peptide-based immunotherapy with malignant tumor.Methods The Hpa sequence was scanned for prediction of the immunogenic peptides-based CTL epitopes using the HLA-binding prediction software SYFPEITHI and BIMAS.Ten the affinity of candidate epitopes to HLA-A2 was evaluated by T2 binding test.Acfivation of T cell was assessed by ELIS-POT and cytotoxictiy by lactate dehydrogenase(LDH)release assay.Results of the six predicted nona-peptides,Hpa(310-318,FLNPDVLDI)showed high affinity of binding to HLA-A2 and led to IFN-γ secre-tion in vitro.Furthermore,Hpa(310-318) FLNPDVILDI could induce PBMC from a HLA-A2 positive healthy donor to lyse specifically HCC-LM6 and SW-480 cells which expressing both Hpa and HLA-A2.Conclusion The nona-peptide Hpa(310-318)FLNPDVLDI may be all HLA-A2-restricted CTL epitope.which is capable of inducing Hpa-specific CTL in vitro.