Study On The CD8+ T Cells Multiepitopes "String-of-beads" Polypeptide Vaccine Of Tuberculosis Antigens

A growing body of evidence derived from both human and non-human models has suggested that CD8+ T lymohocytes play an essential and unique role in protection against Mycobacterial tuberculosis (Mtb.), especially in controlling latent or persist infection. Therefore, identification of MHC-I-restricted mycobacterial epitopes can be of considerable interest in the investigation of CD8+ T cells immunity during Mtb. infection and in the developing an effective vaccine against TB. In this study, we predicted and identified HLA-A*0201 restricted CD8+ CTL epitopes in Mtb. antigen Rv0309 and Rv0173, made the construct joining 6 CTL epitopes, a PADAE and a Trojan antigen, a signal sequence, via furin-sensitive linkers, expressed the recombinant "string-of-bead" multiepitopes polypeptide in E.coli., further studied its immunogenecity in a human cell model. The results showed that peptides of RLLALLCAAV (3～12aa) and RLSQSADQYL (21-30aa), KLILTQPFDV (302-311aa) were HLA-A*0201 restricted CD8+ CTL immunodominant epitopes to Rv0309 and Rv0173 respectively. The recombinant "string-of-bead" multiepitopes polypeptide we obtained in this study could elicit stronger CTL protective immune responses than single peptide and PPD.