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CD20 alternative splicing isoform generates immunogenic CD 4 helper T epitopes
Author(s) -
Vauchy Charline,
Gamonet Clementine,
Ferrand Christophe,
Daguindau Etienne,
Galaine Jeanne,
Beziaud Laurent,
Chauchet Adrien,
Henry Dunand Carole J.,
Deschamps Marina,
Rohrlich Pierre Simon,
Borg Christophe,
Adotevi Olivier,
Godet Yann
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29366
Subject(s) - epitope , cd20 , b cell , antigen , biology , immune system , cd8 , immunotherapy , cancer research , microbiology and biotechnology , immunology , antibody
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.