Abstract

Abstract High affinity T cell receptors (TCRs) are absent from the native T cell repertoire. While current hypotheses propose that high affinity TCRs are more sensitive to antigen and have a competitive advantage in immune responses, emerging evidence suggests that higher affinity T cells may reach a threshold where they experience decreased functionality, loss of binding specificity, and become prone to anergy. High affinity TCRs are especially attractive to facilitate immunotherapies as native TCR binding affinity may be too low to effectively initiate activation. However, the effects of increased TCR affinity for CD4+ T cells specific for naturally occurring epitopes is poorly understood. To address this question, we engineered via yeast display several class II-restricted high affinity TCRs specific for a naturally occurring peptide from Listeria monocytogenes protein listeriolysin O. Our high affinity clones have KD values as low as 8.7 nM and half-lives as long as 174 minutes when measured by tetramer dissociation assays. This panel of class II restricted high affinity TCRs specific for a naturally occurring Listeria monocytogenes epitope provides a novel means of testing the role of affinity and CD4+ T cell activation responses in the context of an infection.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call