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CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes.

Abstract
Cancer-specific splice variants gain significant interest as they generate neo-antigens that could be targeted by immune cells. CD20, a membrane antigen broadly expressed in mature B cells and in B cell lymphomas, is subject to an alternative splicing named D393-CD20 leading to loss of membrane expression of the spliced isoform. D393-CD20 expression is detectable in transformed B cells and upregulated in various lymphoma B cells. In this study, we show that D393-CD20 is translated in malignant B cells and that D393-CD20 specific CD4 T cells producing IFN-γ are present in B-cell lymphoma patients. Then, we have investigated whether the 20mer D393-CD20 peptide spanning the splicing site might be targeted by the immune system and we have shown that D393-CD20-specific CD4 Th1 clones could directly recognize malignant B cell lines and kill autologous lymphoma B cells indicating that D393-CD20-derived epitopes are naturally processed and presented on tumor cells. Finally, D393-CD20 peptide-based vaccination induced specific CD8 and CD4 T cell responses in HLA-humanized transgenic mice suggesting the presentation of D393-CD20 derived peptides on both HLA Class-I and -II. These findings support further investigations on the potential use of D393-CD20 directed specific immunotherapy in B cell malignancies.
AuthorsCharline Vauchy, Clementine Gamonet, Christophe Ferrand, Etienne Daguindau, Jeanne Galaine, Laurent Beziaud, Adrien Chauchet, Carole J Henry Dunand, Marina Deschamps, Pierre Simon Rohrlich, Christophe Borg, Olivier Adotevi, Yann Godet
JournalInternational journal of cancer. Journal international du cancer (Int J Cancer) Vol. 137 Issue 1 Pg. 116-26 (Jul 1 2015) ISSN: 1097-0215 [Electronic] United States
PMID25449106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 UICC.
Chemical References
  • Antigens, CD20
  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • Peptides
  • Protein Isoforms
Topics
  • Alternative Splicing
  • Animals
  • Antigens, CD20 (genetics, immunology)
  • Antigens, Neoplasm (genetics, immunology)
  • Cell Line, Tumor
  • Epitopes, T-Lymphocyte (immunology)
  • Humans
  • Immunization
  • Lymphoma, B-Cell (genetics, immunology, therapy)
  • Mice
  • Mice, Transgenic
  • Peptides (administration & dosage, immunology)
  • Protein Isoforms (genetics, metabolism)
  • T-Lymphocytes, Helper-Inducer (immunology)

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