Abstract B078: Unbiased identification of CD4+ T-cell epitopes using novel MHC-based chimeric receptors

αβT-cell receptors (TCRs) bind peptide-major histocompatibility complexes (pMHC) with low affinity, posing a considerable challenge for direct identification of αβT-cell cognate peptides (epitopes). Here, we describe a platform for the discovery of MHC class-II presented epitopes, based on screening of engineered reporter cells expressing novel pMHC-TCR (MCR) hybrid molecules carrying cDNA-derived peptides. This technology identifies natural epitopes of CD4 T-cells in an unbiased and efficient manner and allows detailed analysis of TCR cross-reactivity providing recognition patterns on top of discrete epitopes. We identify cognate peptides of virus- and tumor-specific T-cells in mouse disease models and present a proof of concept for human T-cells. Furthermore, we show that vaccination with a peptide naturally recognized by TILs can efficiently protect from tumor challenge. Thus, the MCR technology holds promise for basic research and clinical applications allowing personalized identification of T-cell antigens in patients. Citation Format: Jan Kisielow, Franz-Josef Obermair, Manfred Kopf. Unbiased identification of CD4+ T-cell epitopes using novel MHC-based chimeric receptors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B078.