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Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers
15:42

Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers

Published on: March 6, 2009

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Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers

Cheryl L Day1, Nilufer P Seth, Michaela Lucas

  • 1Howard Hughes Medical Institute, Partners AIDS Research Center, Boston, Massachusetts, USA.

The Journal of Clinical Investigation
|September 17, 2003
PubMed

Insights

Researchers identified hepatitis C virus (HCV)-specific CD4 T cells in patients who recovered from HCV infection. This breakthrough allows studying rare T cells, offering insights into viral clearance and immune surveillance in chronic infections.

Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Chronic viral infections, like hepatitis C virus (HCV), are linked to persistent virus-specific CD4 T cells.
  • Ex vivo characterization of these circulating CD4 T cells has been a significant challenge in understanding immune responses.

Purpose of the Study:

  • To develop a novel method for characterizing rare, circulating virus-specific CD4 T cells.
  • To investigate the phenotype and function of CD4 T cells in individuals with resolved or chronic HCV infection.

Main Methods:

  • Developed a novel approach using MHC class II/peptide tetramers generated via cellular peptide exchange.
  • Expressed HLA-DR molecules with a cleavable CLIP peptide for efficient viral peptide exchange.
  • Isolated HCV tetramer-labeled CD4 T cells using magnetic bead capture from peripheral blood.

Main Results:

  • Successfully isolated HCV-specific CD4 T cells from individuals with spontaneous HCV resolution, but not from those with chronic infection.
  • These cells were found at very low frequencies (1:1,200 to 1:111,000) and expressed surveillance markers (CCR7+CD45RA-CD27+).
  • The identified T cells exhibited a restricted Vbeta repertoire, indicating significant in vivo selection.

Conclusions:

  • Demonstrated a correlation between clinical outcome (viral clearance) and the presence of circulating HCV-specific CD4 T cells.
  • Established a method for studying rare memory CD4 T cell populations ex vivo in human viral diseases.
  • Provides a foundation for understanding CD4 T cell roles in viral persistence and resolution.

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