Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections

Banu, Nasirah; Chia, Adeline; Ho, Zi Zong; Garcia, Alfonso Tan; Paravasivam, Komathi; Grotenbreg, Gijsbert M.; Bertoletti, Antonio; Gehring, Adam J.

Our data suggests that TLR ligands help polarize T cells during the activation phase through reduced production of regulatory and Th2associated cytokines and increased the production of inflammatory and Th1-associated cytokines. Not all IFN-c1 T cell stained positive with HLA pentamers, indicating that cells that do not express enough properly paired TCR to bind HLA mulitmers but remained functional. This was confirmed by co-staining IFN-c1 T cells with TCR beta chain antibodies. Approximately 90% or greater of the IFN-c1 T cells were also positive for the introduced beta chain, suggesting that nearly all responding cells are epitope-specific through the introduced TCR. It has been established that T cells remain functional with only a fraction of their TCR on the surface, as low at 5% in one study 36 . Thus, the use of TLR ligands during T cell activation may help to maximize the pool of functional T cells for adoptive cell therapy.