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Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes.
FASEB J. 1998 Oct; 12(13):1349-57.FJ

Abstract

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 alpha/beta-TCR, gamma/delta-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, alpha/beta-TCR, and gamma/delta-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, alpha/beta-TCR, and gamma/delta-TCR at the basal membrane of enterocytes that were interdigitated by extensions of lymphocytes. In situ hybridization experiments revealed that CD8 and gamma/delta-TCR were not expressed by CD enterocytes. We conclude that CD8, alpha/beta-TCR, and gamma/delta-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, alpha/beta-TCR, and gamma/delta-TCR by the basolateral membrane of small intestinal enterocytes.

Authors+Show Affiliations

Universitätskinderklinik, D-48149 Münster, Germany. zimmerp@uni-muenster.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9761778

Citation

Zimmer, K P., et al. "Targeting of Gliadin Peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi Complexes and Vacuoles Within Celiac Disease Enterocytes." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 12, no. 13, 1998, pp. 1349-57.
Zimmer KP, Naim H, Weber P, et al. Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes. FASEB J. 1998;12(13):1349-57.
Zimmer, K. P., Naim, H., Weber, P., Ellis, H. J., & Ciclitira, P. J. (1998). Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 12(13), 1349-57.
Zimmer KP, et al. Targeting of Gliadin Peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi Complexes and Vacuoles Within Celiac Disease Enterocytes. FASEB J. 1998;12(13):1349-57. PubMed PMID: 9761778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes. AU - Zimmer,K P, AU - Naim,H, AU - Weber,P, AU - Ellis,H J, AU - Ciclitira,P J, PY - 1998/10/8/pubmed PY - 1998/10/8/medline PY - 1998/10/8/entrez SP - 1349 EP - 57 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 12 IS - 13 N2 - 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 alpha/beta-TCR, gamma/delta-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, alpha/beta-TCR, and gamma/delta-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, alpha/beta-TCR, and gamma/delta-TCR at the basal membrane of enterocytes that were interdigitated by extensions of lymphocytes. In situ hybridization experiments revealed that CD8 and gamma/delta-TCR were not expressed by CD enterocytes. We conclude that CD8, alpha/beta-TCR, and gamma/delta-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, alpha/beta-TCR, and gamma/delta-TCR by the basolateral membrane of small intestinal enterocytes. SN - 0892-6638 UR - https://www.unboundmedicine.com/medline/citation/9761778/Targeting_of_gliadin_peptides_CD8_alpha/beta_TCR_and_gamma/delta_TCR_to_Golgi_complexes_and_vacuoles_within_celiac_disease_enterocytes_ L2 - https://doi.org/10.1096/fasebj.12.13.1349 DB - PRIME DP - Unbound Medicine ER -