Healthy cells functionally present TAP-independent SSR1 peptides: implications for selection of clinically relevant antigens [article]

Antonius A. de Waard, Tamara Verkerk, Kelly Hoefakker, Dirk M. van der Steen, Marlieke L.M. Jongsma, Sophie Bliss, Arnoud H. de Ru, Peter A. van Veelen, Marieke Griffioen, Mirjam H.M. Heemskerk, Robbert M. Spaapen
2020 bioRxiv   pre-print
AbstractTumors with an impaired transporter associated with antigen processing (TAP) present several ER-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. Selection of such TAP-independent antigens for T cell-based immunotherapy should include analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. However, it is unknown how the absence of clinically relevant antigens on healthy cells needs to be validated. Here we monitored
more » ... e we monitored TAP-independent antigen presentation on various healthy cells using a new toolbox consisting of a T cell clone recognizing a TAP-independent SSR1-derived antigen. We found that most but not all healthy cells present this antigen under normal and inflammatory conditions, indicating that TAP-independent antigen presentation is a variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety of healthy cell types to define clinically relevant TAP-independent antigens that can be safely targeted by immunotherapy.
doi:10.1101/2020.06.11.146449 fatcat:bll2jk46ofamdctvhorx6m5k54