Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes

Ebstein F, Textoris-Taube K, Keller C, Golnik R, Vigneron N, Van Den Eynde BJ, Schuler-Thurner B, Schadendorf D, Lorenz FKM, Uckert W, Urban S, Lehmann A, Albrecht-Koepke N, Janek K, Henklein P, Niewienda A, Kloetzel PM, Mishto M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 6

Pages Range: 24032

DOI: 10.1038/srep24032

Abstract

Proteasome-catalyzed peptide splicing represents an additional catalytic activity of proteasomes contributing to the pool of MHC-class I-presented epitopes. We here biochemically and functionally characterized a new melanoma gp100 derived spliced epitope. We demonstrate that the gp100(mel)47-52/40-42 antigenic peptide is generated in vitro and in cellulo by a not yet described proteasomal condensation reaction. gp100(mel)47-52/40-42 generation is enhanced in the presence of the ?5i/LMP7 proteasome-subunit and elicits a peptide-specific CD8(+) T cell response. Importantly, we demonstrate that different gp100(mel)-derived spliced epitopes are generated and presented to CD8(+) T cells with efficacies comparable to non-spliced canonical tumor epitopes and that gp100(mel)-derived spliced epitopes trigger activation of CD8(+) T cells found in peripheral blood of half of the melanoma patients tested. Our data suggest that both transpeptidation and condensation reactions contribute to the frequent generation of spliced epitopes also in vivo and that their immune relevance may be comparable to non-spliced epitopes.

Authors with CRIS profile

Beatrice Schuler-Thurner Lehrstuhl für Haut- und Geschlechtskrankheiten

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Université Catholique de Louvain (UCL) BE Belgium (BE) Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Ebstein, F., Textoris-Taube, K., Keller, C., Golnik, R., Vigneron, N., Van Den Eynde, B.J.,... Mishto, M. (2016). Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes. Scientific Reports, 6, 24032. https://doi.org/10.1038/srep24032

MLA:

Ebstein, F., et al. "Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes." Scientific Reports 6 (2016): 24032.

BibTeX: Download