31Tumors with an impaired transporter associated with antigen processing (TAP) present 32 several ER-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. 33Selection of such TAP-independent antigens for T cell-based immunotherapy should include 34 analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. 35However, it is unknown how the absence of clinically relevant antigens on healthy cells needs 36 to be validated. Here we monitored TAP-independent antigen presentation on various healthy 37 cells using a new toolbox consisting of a T cell clone recognizing a TAP-independent SSR1-38 derived antigen. We found that most but not all healthy cells present this antigen under normal 39 and inflammatory conditions, indicating that TAP-independent antigen presentation is a 40 variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety 41 of healthy cell types to define clinically relevant TAP-independent antigens that can be safely 42 targeted by immunotherapy. 43