Extracellular domains of CD8α and CD8ß subunits are sufficient for HLA class I restricted helper functions of TCR-engineered CD4(+) T cells

PLoS One. 2013 May 30;8(5):e65212. doi: 10.1371/journal.pone.0065212. Print 2013.

Abstract

By gene transfer of HLA-class I restricted T-cell receptors (TCRs) (HLA-I-TCR) into CD8(+) as well as CD4(+) T-cells, both effector T-cells as well as helper T-cells can be generated. Since most HLA-I-TCRs function best in the presence of the CD8 co-receptor, the CD8αß molecule has to be co-transferred into the CD4(+) T-cells to engineer optimal helper T-cells. In this study, we set out to determine the minimal part of CD8αβ needed for optimal co-receptor function in HLA-I-TCR transduced CD4(+) T-cells. For this purpose, we transduced human peripheral blood derived CD4(+) T-cells with several HLA-class I restricted TCRs either with or without co-transfer of different CD8 subunits. We demonstrate that the co-transduced CD8αβ co-receptor in HLA-I-TCR transduced CD4(+) T-cells behaves as an adhesion molecule, since for optimal antigen-specific HLA class I restricted CD4(+) T-cell reactivity the extracellular domains of the CD8α and ß subunits are sufficient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8 Antigens / chemistry
  • CD8 Antigens / metabolism*
  • Cell Engineering / methods*
  • Extracellular Space / metabolism
  • HLA Antigens / genetics
  • HLA Antigens / metabolism*
  • Humans
  • Interferon-gamma / biosynthesis
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology*
  • Transfection

Substances

  • CD8 Antigens
  • CD8alpha antigen
  • CD8beta antigen
  • HLA Antigens
  • Protein Subunits
  • Receptors, Antigen, T-Cell
  • Interferon-gamma

Grant support

This work was supported by the Dutch Cancer Society (NKB 2007-3927) and ZonMw (grant ZonMw 433.00.001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.