Cancer-specific T helper shared and neo-epitopes uncovered by expression of the MHC class II master regulator CIITA

Hos, B.J.; Tondini, E.; Camps, M.G.M.; Rademaker, W.; Bulk, J. van den; Ruano, D.; Janssen, G.M.C.; Ru, A.H. de; Elsen, P.J. van den; Miranda, N.F.C.C. de; Veelen, P.A. van; Ossendorp, F.

doi:doi:10.1016/j.celrep.2022.111485

We report an approach to identify tumor-specific CD4⁺T cell neo-epitopes of both mouse and human cancer cells by analysis of MHC class II-eluted natural peptides. MHC class II-presented peptide sequences are identified by introducing the MHC class II transactivator CIITA in tumor cells that were originally MHC class II-negative. CIITA expression facilitates cell-surface expression of MHC class II molecules and the appropriate peptide-loading machinery. Peptide elution of purified MHC class II molecules and subsequent mass spectrometry reveals many novel oncoviral-, shared and neo-epitopes. Immunological relevance of these epitopes is shown by natural presentation by dendritic cells and immunogenicity. Synthetic peptide vaccination induced functional CD4⁺ T cell responses which helped tumor control in vivo. Thus, this CIITA transfection approach aids to identify relevant T helper epitopes presented by any MHC class II allele that would be otherwise...Show moreWe report an approach to identify tumor-specific CD4⁺T cell neo-epitopes of both mouse and human cancer cells by analysis of MHC class II-eluted natural peptides. MHC class II-presented peptide sequences are identified by introducing the MHC class II transactivator CIITA in tumor cells that were originally MHC class II-negative. CIITA expression facilitates cell-surface expression of MHC class II molecules and the appropriate peptide-loading machinery. Peptide elution of purified MHC class II molecules and subsequent mass spectrometry reveals many novel oncoviral-, shared and neo-epitopes. Immunological relevance of these epitopes is shown by natural presentation by dendritic cells and immunogenicity. Synthetic peptide vaccination induced functional CD4⁺ T cell responses which helped tumor control in vivo. Thus, this CIITA transfection approach aids to identify relevant T helper epitopes presented by any MHC class II allele that would be otherwise very difficult to predict and reveals important new targets for cancer immunotherapy.Show less

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Cancer-specific T helper shared and neo-epitopes uncovered by expression of the MHC class II master regulator CIITA

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