T cells recognizing a 11mer influenza peptide complexed to H‐2D^b show promiscuity for peptide length

Abstract

T-cell repertoire is selected according to self peptide-MHC (major histocompatibility complex) complexes in the thymus. Although most peripheral T cells recognize specific pathogen-derived peptides complexed to self-MHC exclusively, some possess cross-reactivity to other self or foreign peptides presented by self-MHC molecules; a phenomenon often termed T-cell receptor (TCR) promiscuity or degeneracy. TCR promiscuity has been attributed to various autoimmune conditions. On the other hand, it is considered a mechanism for a relatively limited TCR repertoire to deal with a potentially much larger antigenic peptide repertoire. Such property has also been utilized to bypass self-tolerance for cancer vaccine development. Although many studies explored such degeneracy for peptide of the same length, few studies reported such properties for peptides of different length. In this study, we finely characterized the CD8(+) T-cell response specific for a 11mer peptide derived from influenza A viral polymerase basic protein 2. The short-term T-cell line, despite possessing highly biased TCR, was able to react with multiple peptides of different length sharing the same core sequence. Out data clearly showed the importance of detailed and quantitative assessments for such T-cell specificity. Our data also emphasize the importance of biochemical demonstration of the naturally presented minimal peptide.

In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma

“…Furthermore, nine HBV genotypes and many variants that have different peptide antigens have been identified to date, 27 and it would be valuable to create one TCR that can specifically recognize several HBV-variant peptide antigens. It is well documented that a TCR can show promiscuity for recognizing a set of variant antigens, [28][29][30][31] but the T cell maintains physiological specificity in the peripheral immune system. We then questioned whether this feature can be harnessed for the generation of affinity-improved TCRs that are capable of recognizing several HBV variants.…”