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Updated: Jul 9, 2026

HLA-Ig Based Artificial Antigen Presenting Cells for Efficient ex vivo Expansion of Human CTL
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Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing

R M Hershberg1, P E Framson, D H Cho

  • 1Immunology and Diabetes Programs, Virginia Mason Research Center, Seattle, Washington 98101, USA. hersh@u.washington.edu

The Journal of Clinical Investigation
|July 1, 1997
PubMed
Summary

Intestinal epithelial cells can present antigens to CD4(+) T cells via HLA class II molecules. Two distinct antigen processing pathways exist, differing with or without gamma-interferon stimulation.

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Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • Intestinal epithelial cells (IECs) express HLA class II molecules, with levels increasing during mucosal inflammation like inflammatory bowel disease.
  • IECs' role as antigen-presenting cells (APCs) for T lymphocytes is crucial for intestinal immunity.

Purpose of the Study:

  • To investigate the molecular mechanisms of HLA class II antigen processing and presentation by IECs.
  • To determine if IECs can function as APCs for CD4(+) T lymphocytes.

Main Methods:

  • Molecular analysis of the HLA class II antigen processing pathway in IECs.
  • Activation of IECs with gamma-interferon (IFN) and assessment of invariant chain and HLA-DM expression.
  • Gene transfer of HLA-DR alleles into IEC lines (HT-29, T84).
  • T cell activation assays using HLA-DR-restricted T cells.

Main Results:

  • IECs possess constitutive levels of cathepsin proteases essential for HLA class II antigen presentation.
  • Gamma-IFN stimulation upregulated invariant chain and HLA-DM, facilitating stable HLA-DR heterodimer formation.
  • IECs efficiently presented antigens to CD4(+) T lymphocytes in a gamma-IFN-dependent manner, similar to conventional APCs.
  • Antigen processing occurred in IECs without gamma-IFN, requiring higher antigen concentrations and unaffected by leupeptin, suggesting a distinct pathway.

Conclusions:

  • IECs utilize two distinct pathways for HLA class II antigen processing.
  • These pathways exhibit differential immunomodulatory properties depending on the presence or absence of mucosal inflammation (gamma-IFN).
  • IECs are capable antigen-presenting cells for CD4(+) T lymphocytes, particularly under inflammatory conditions.