Proteomics

Dataset Information

0

Phage display enables machine learning discovery of cancer antigen specific TCRs

ABSTRACT: T cells targeting epitopes in infectious diseases or cancer play a central role in spontaneous and therapy-induced immune responses. T-cell epitope recognition is mediated by the binding of the T-Cell Receptor (TCR) and TCRs recognizing clinically relevant epitopes are promising for T-cell based therapies. Starting from one of the few known TCRs targeting the cancer-testis antigen NY-ESO-1 (157–165) epitope, we built large phage display libraries of TCRs with randomized Complementary Determining Region 3 of the β chain. The TCR libraries were panned against the NY-ESO-1 epitope, which enabled us to collect thousands of epitope-specific TCR sequences. We then trained a machine learning TCR-epitope interaction predictor with this data and could identify several epitope-specific TCRs directly from TCR repertoires. Cellular binding and functional assays revealed that the predicted TCRs displayed activity towards the NY-ESO-1 epitope and no detectable cross-reactivity with self-peptides. Overall, our work demonstrates how display technologies combined with machine learning models of TCR-epitope recognition can effectively leverage large TCR repertoires for TCR discovery.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Michal Bassani-Sternberg  

LAB HEAD: Michal Bassani-Sternberg

PROVIDER: PXD058478 | Pride | 2025-06-20

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
20241111_DIA_COL059-00001-HLAIp_R03.raw Raw
20241111_DIA_COL059-00001-HLAIp_R04.raw Raw
20241111_DIA_COL059-00002-HLAIp_R03.raw Raw
20241111_DIA_COL059-00002-HLAIp_R04.raw Raw
20241111_DIA_COL059-00003-HLAIp_R03.raw Raw
Items per page:
1 - 5 of 14
altmetric image

Publications

T cells targeting epitopes in infectious diseases or cancer play a central role in spontaneous and therapy-induced immune responses. Epitope recognition is mediated by the binding of the T cell receptor (TCR), and TCRs recognizing clinically relevant epitopes are promising for T cell-based therapies. Starting from a TCR targeting the cancer-testis antigen NY-ESO-1<sub>157-165</sub> epitope, we built large phage display libraries of TCRs with randomized complementary determining region 3 of the β  ...[more]