Natural antigenic peptides from squamous cell carcinoma recognized by autologous HLA-DR8-restricted CD4+ T cells

Hiroaki Kondo1, Hiroeki Sahara, Akihiro Miyazaki

  • 1Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.

Insights

Researchers identified a novel CD4+ T cell target antigen in oral squamous cell carcinoma (SCC). This discovery advances understanding of tumor immunity and potential therapeutic strategies for SCC.

Area of Science:

  • Immunology
  • Oncology
  • Biochemistry

Background:

  • CD8+ T cell tumor antigens are well-characterized, but CD4+ T cell targets remain largely unknown.
  • Previous work identified an oral squamous cell carcinoma (SCC) cell line (OSC-20) lysed by autologous CD4+ T cells (TcOSC-20) restricted by HLA-DRB1*08032 (HLA-DR8).

Purpose of the Study:

  • To identify specific tumor antigens recognized by CD4+ T cells in oral squamous cell carcinoma.
  • To investigate the potential of these antigens as therapeutic targets for SCC.

Main Methods:

  • Tumor cell lysate purification using two-step chromatography.
  • Mass spectrometry (LC/MS/MS) analysis of purified fractions.
  • Peptide synthesis and T cell cytotoxic response assays.

Main Results:

  • One RP-HPLC fraction showed significant T cell recognition.
  • Six potential peptide antigens were identified via LC/MS/MS.
  • A peptide corresponding to human alpha-enolase (residues 321-336) elicited a strong cytotoxic response from TcOSC-20 cells.

Conclusions:

  • Squamous cell carcinoma cells process and present endogenous gene products on HLA class II molecules.
  • These presented antigens can serve as target molecules for autologous CD4+ T cells.
  • Human alpha-enolase is a potential CD4+ T cell target antigen in oral SCC.

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