Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing

Robert M. Hershberg, Paul E. Framson, Diane H. Cho, Lawrence Y. Lee, Susan Kovats, Jill Beitz, Janice S. Blum, Gerald T. Nepom

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177 Scopus citations

Abstract

Intestinal epithelial cells express a low level of HLA class II molecules constitutively, with elevated levels seen in the setting of mucosal inflammation including inflammatory bowel disease. The ability of intestinal epithelial cells to act as antigen presenting cells for αβ CD4+ T lymphocytes was examined through a molecular analysis of the HLA class II antigen processing pathway. We have shown that intestinal epithelial cells contain abundant constitutive levels of the cathepsin proteases proven to function in HLA class II mediated antigen presentation. Activation of these cells by γ-IFN induced the expression of invariant chain and HLA-DM αβ, thus facilitating the formation of compact, SDS-stable HLA-DR αβ heterodimers. Using HLA-DR-restricted T cells and retrovital mediated gene transfer of HLA-DR alleles into the intestinal epithelial cell lines HT-29 and T84, we demonstrated efficient antigen processing and presentation to CD4+ T lymphocytes in the presence of the proinflammatory cytokine γ-IFN. The class II processing pathway and presentation in the presence of γ-IFN was indistinguishable from that observed with a conventional antigen presenting cell. Antigen processing also occurred in intestinal epithelial cells in the absence of γ-IFN, and in contrast to that seen after stimulation with γ-IFN, required high concentration of antigen and was not inhibited by the protease inhibitor leupeptin. These data suggest the use of two distinct pathways of HLA class II antigen processing in enterocytes with differential immunomodulatory properties in the presence or absence of mucosal inflammation.

Original languageEnglish (US)
Pages (from-to)204-215
Number of pages12
JournalJournal of Clinical Investigation
Volume100
Issue number1
DOIs
StatePublished - Jul 1 1997

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Keywords

  • Antigen presentation
  • Human
  • Inflammatory bowel disease
  • Intestinal mucosa
  • T lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hershberg, R. M., Framson, P. E., Cho, D. H., Lee, L. Y., Kovats, S., Beitz, J., Blum, J. S., & Nepom, G. T. (1997). Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing. Journal of Clinical Investigation, 100(1), 204-215. https://doi.org/10.1172/JCI119514