Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients

Cancer Immunol Immunother. 2019 Oct;68(10):1561-1572. doi: 10.1007/s00262-019-02389-7. Epub 2019 Sep 7.


Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4+ T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are largely unknown. In this study, we have characterized human CD20-derived epitopes restricted by HLA-DR1, HLA-DR3, HLA-DR4, and HLA-DR7, and investigated whether T cell responses directed against CD20-derived peptides can be elicited in human HLA-DR-transgenic mice and human samples. Based on in vitro binding assays to recombinant human MHC II molecules and on in vivo immunization assays in H-2 KO/HLA-A2+-DR1+ transgenic mice, we have identified 21 MHC II-restricted long peptides derived from intracellular, membrane, or extracellular domains of the human non-mutated CD20 protein that trigger in vitro IFN-γ production by PBMCs and splenocytes from healthy individuals and by PBMCs from follicular lymphoma patients. These CD20-derived MHC II-restricted peptides could serve as a therapeutic tool for improving and/or monitoring anti-CD20 T cell activity in patients treated with rituximab or other anti-CD20 antibodies.

Keywords: CD4+ T cell responses; Follicular lymphoma; Human CD20-derived peptides; Non-mutated self-peptides.

MeSH terms

  • Animals
  • Antigens, CD20 / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • HLA-DRB1 Chains / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Lymphoma / drug therapy*
  • Lymphoma / immunology
  • Mice
  • Rituximab / therapeutic use


  • Antigens, CD20
  • HLA-DRB1 Chains
  • Rituximab
  • Interferon-gamma