Targeting of gliadin peptides, CD8, /ß-TCR, and /-TCR to Golgi complexes and vacuoles within celiac disease enterocytes

^a Universitätskinderklinik, D-48149 Münster, Germany
^b Institut für physiologische Chemie, Tierärztliche Hochschule, D-30559 Hannover, Germany
^c Gastroenterology Unit (UMDS),St. Thomas' Hospital, London SEI 7EH, U.K.

Celiac disease (CD) is characterized by autodestruction of enterocytes after exposure of genetically susceptible individuals to dietary gluten. To define the transport pathways of proteins involved in the celiac immune response, we wished to determine the subcellular compartments of the intestinal mucosa where wheat gliadin peptides colocalize with receptors of T lymphocytes, including /ß-TCR, /-TCR, and CD8. Semithin and ultrathin frozen section of jejunal biopsies from CD patients and controls were used to perform immunofluorescence and immunogold labeling as well as in situ hybridization experiments. In patients with active CD, we detected gliadin peptides in vacuoles and Golgi complexes of enterocytes. CD8, /ß-TCR, and /-TCR were found in vacuoles and Golgi complexes within these gliadin-containing enterocytes in addition to the surface of intraepithelial and mucosal T lymphocytes. In contrast, we observed that the localization of CD4, CD3, T cell-restricted intracellular antigen (TIA), and leukocyte common antigen (LCA) was restricted to lymphocytes in CD patients. We further detected labeling signals for gliadin peptides, CD8, /ß-TCR, and /-TCR at the basal membrane of enterocytes that were interdigitated by extensions of lymphocytes. In situ hybridization experiments revealed that CD8 and /-TCR were not expressed by CD enterocytes. We conclude that CD8, /ß-TCR, and /-TCR are targeted to Golgi complexes and vacuoles of small intestinal enterocytes in active CD. The observed process may be involved in the pathogenesis of CD enterocytes. We propose a mechanism for the uptake of CD8, /ß-TCR, and /-TCR by the basolateral membrane of small intestinal enterocytes.—Zimmer, K.-P., Naim, H., Weber, P., Ellis, H. J., Ciclitira. P. J. Targeting of gliadin peptides, CD8, /ß-TCR, and /-TCR to Golgi complexes and vacuoles within celiac disease enterocytes. FASEB J: 12, 1349–1357 (1998)

Key Words: endoplasmic reticulum • T cell receptor • trans-Golgi network

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