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A calcium binding protein, S100A4, mediates T cell dependent cytotoxicity as a transformation-associated antigen

Nobuhiko Kondo1, Shingo Ichimiya, Yasuaki Tamura

  • 1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.

Microbiology and Immunology
|January 25, 2005
PubMed

Insights

The calcium-binding protein S100A4 is identified as a potential target molecule for T cell receptor gamma delta (TCR γδ) T cell-mediated lysis. This finding advances understanding of TCR γδ T cell recognition of tumor-associated antigens.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • The target molecule for T cell receptor gamma delta (TCR γδ) T cell-mediated lysis is currently unknown.
  • A previously identified #067 antigen on fibrosarcoma cells is implicated as a target for TCR γδ T cells.
  • #067 monoclonal antibody (mAb) inhibits TCR γδ T cell lysis of #067-positive cells.

Purpose of the Study:

  • To identify the protein sequence of the #067 antigen.
  • To investigate the role of S100A4 as a potential target molecule for TCR γδ T cell-mediated lysis.

Main Methods:

  • Molecular cloning techniques were employed to identify the #067 antigen.
  • Expression levels of S100A4 were analyzed at transcription and protein levels.
  • Flow cytometry and immunocytochemistry were used to assess co-localization.
  • Inhibition assays using rabbit anti-S100A4 polyclonal antibodies (pAb) were performed.

Main Results:

  • Molecular cloning suggested that S100A4 is the #067 antigen.
  • S100A4 expression was significantly higher in H-ras oncogene-transformed fibrosarcoma W31 cells compared to normal WFB cells.
  • #067 antigen partially co-localized with S100A4 in both the cytoplasm and on the cell surface of W31 cells.
  • Anti-S100A4 pAb inhibited TCR γδ T cell-mediated lysis of #067-positive cells.

Conclusions:

  • S100A4 is a likely candidate for the #067 antigen.
  • S100A4 may function as a target molecule for TCR γδ T cell-mediated lysis.
  • Further investigation is needed to elucidate the precise mechanism of S100A4 involvement in TCR γδ T cell recognition.

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