Increase Of The Sensitivity Of Cytotoxic T Lymphocytes To Antigenic Stimulation By DNA Prime/recombinant Viral Vector Boost Immunization

Cytotoxic T lymphocytes (CTLs) play an important role in fighting against a number of infectious diseases, including HIV/AIDS. CTLs kill virus-infected cells upon recognition of antigenic peptides presented in the context of MHC-I molecules. High-avidity CTLs are able to destruct infected cells at lower concentration of peptide-MHC complex, thereby effectively containing the spread of viruses. Therefore, the generation of high-avidity T cells is one of the crucial criteria to determine the success of immunization strategies. DNA prime-viral vector boost has been widely used and shown to be able to elicit high-avidity CTLs in vivo; however, it remains unknown on the mechanism underlying this observation. To address this question, the functional avidity was dissected into two parts in our experiments: TCR affinity for peptide-MHC and activation threshold of CTLs. TCR avidity of CD8+ T cells were compared after mice received DNA prime-rVV boost (PB), three (3DNA) or four (4DNA) inoculations of DNA vaccine. No differences were observed in tetramer binding capacity between PB and 4DNA, but both were significantly higher than that receiving 3DNA. Analysis of T cell receptor repertoire showed that epitope specific CTLs in mice received PB and 4DNA express narrower range of TCR than those received 3DNA, indicating that a selection of TCR repertoire occurred with the increase of vaccine inoculations. Despite the property of TCR in PB group is similar to those in 4DNA group, the CTLs in PB group were more sensitive to stimulation delivered by anti-CD3εchain mAb. Therefore, in DNA prime-rVV boost...