TY - JOUR
T1 - Healthy cells functionally present TAP-independent SSR1 peptides
T2 - implications for selection of clinically relevant antigens
AU - de Waard, Antonius A
AU - Verkerk, Tamara
AU - Hoefakker, Kelly
AU - van der Steen, Dirk M
AU - Jongsma, Marlieke L M
AU - Melamed Kadosh, Dganit
AU - Bliss, Sophie
AU - de Ru, Arnoud H
AU - Admon, Arie
AU - van Veelen, Peter A
AU - Griffioen, Marieke
AU - Heemskerk, Mirjam H M
AU - Spaapen, Robbert M
N1 - © 2021 The Author(s).
PY - 2021/2/19
Y1 - 2021/2/19
N2 - Tumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-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 TAP-independent antigen presentation on various healthy cells after establishing a T cell tool recognizing a TAP-independent signal sequence receptor 1-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.
AB - Tumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-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 TAP-independent antigen presentation on various healthy cells after establishing a T cell tool recognizing a TAP-independent signal sequence receptor 1-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.
U2 - https://doi.org/10.1016/j.isci.2021.102051
DO - https://doi.org/10.1016/j.isci.2021.102051
M3 - Article
C2 - 33554062
SN - 2589-0042
VL - 24
SP - 102051
JO - iScience
JF - iScience
IS - 2
ER -