Abstract
HLA-DR and T6 surface antigens are expressed only by Langerhans cells and indeterminate cells in normal human epidermis. We have previously demonstrated that T6 antigens are internalized in Langerhans cells and indeterminate cells by receptor-mediated endocytosis. This process is induced by the binding of BL6, a monoclonal antibody directed against T6 antigens. In the present study, using a monoclonal antibody directed against HLA-DR antigens, on human epidermal cells in suspension, we show that the surface HLA-DR antigens are also internalized by receptor-mediated endocytosis in Langerhans and indeterminate cells. Moreover, using immunogold double labeling, we demonstrate that T6 and HLA-DR antigens are internalized through common coated regions of the membrane of Langerhans or indeterminate cells. The receptor-mediated endocytosis that is induced involves coated pits and vesicles, receptosomes, lysosomes, and also, in Langerhans cells, the Birbeck granules. Thus, T6 antigens, which are considered to be "unusual" or "nonclassical" major histocompatibility complex class I molecules, and the major histocompatibility complex class II molecules, HLA-DR, are internalized in Langerhans and indeterminate cells through common receptor-mediated endocytosis organelles.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bhan A. K., Reinherz E. L., Poppema S., McCluskey R. T., Schlossman S. F. Location of T cell and major histocompatibility complex antigens in the human thymus. J Exp Med. 1980 Oct 1;152(4):771–782. doi: 10.1084/jem.152.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calabi F., Milstein C. A novel family of human major histocompatibility complex-related genes not mapping to chromosome 6. Nature. 1986 Oct 9;323(6088):540–543. doi: 10.1038/323540a0. [DOI] [PubMed] [Google Scholar]
- Carpentier J. L., Gorden P., Anderson R. G., Goldstein J. L., Brown M. S., Cohen S., Orci L. Co-localization of 125I-epidermal growth factor and ferritin-low density lipoprotein in coated pits: a quantitative electron microscopic study in normal and mutant human fibroblasts. J Cell Biol. 1982 Oct;95(1):73–77. doi: 10.1083/jcb.95.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chan C. C., Mochizuki M., Palestine A. G., BenEzra D., Gery I., Nussenblatt R. B. Kinetics of T-lymphocyte subsets in the eyes of Lewis rats with experimental autoimmune uveitis. Cell Immunol. 1985 Dec;96(2):430–434. doi: 10.1016/0008-8749(85)90373-9. [DOI] [PubMed] [Google Scholar]
- Chu A., Eisinger M., Lee J. S., Takezaki S., Kung P. C., Edelson R. L. Immunoelectron microscopic identification of Langerhans cells using a new antigenic marker. J Invest Dermatol. 1982 Feb;78(2):177–180. doi: 10.1111/1523-1747.ep12506352. [DOI] [PubMed] [Google Scholar]
- Cohen J. H., Bouveret E., Pluot M., Revillard J. P. Characterization of Langerhans' cells using a monoclonal anti-HLA-DR (Ia-like) antibody. Arch Pathol Lab Med. 1981 Aug;105(8):438–438. [PubMed] [Google Scholar]
- Dezutter-Dambuyant C., Cordier G., Schmitt D., Faure M., Laquoi C., Thivolet J. Quantitative evaluation of two distinct cell populations expressing HLA-DR antigens in normal human epidermis. Br J Dermatol. 1984 Jul;111(1):1–11. doi: 10.1111/j.1365-2133.1984.tb04010.x. [DOI] [PubMed] [Google Scholar]
- Dezutter-Dambuyant C., Faure M., Schmitt D., Laquoi C., Thivolet J. Simultaneous detection of T6 and HLA-DR antigens distinguishes three cell subpopulations in dispersed normal human epidermal cells. Immunol Lett. 1984;7(4):203–207. doi: 10.1016/0165-2478(84)90044-0. [DOI] [PubMed] [Google Scholar]
- Dezutter-Dambuyant C., Schmitt D., Faure M., Horisberger M., Thivolet J. Immunogold technique applied to simultaneous identification of T6 and HLA-DR antigens on Langerhans cells by electron microscopy. J Invest Dermatol. 1985 Jun;84(6):465–468. doi: 10.1111/1523-1747.ep12272371. [DOI] [PubMed] [Google Scholar]
- Dickson R. B., Willingham M. C., Pastan I. alpha 2-macroglobulin adsorbed to colloidal gold: a new probe in the study of receptor-mediated endocytosis. J Cell Biol. 1981 Apr;89(1):29–34. doi: 10.1083/jcb.89.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Faulk W. P., Taylor G. M. An immunocolloid method for the electron microscope. Immunochemistry. 1971 Nov;8(11):1081–1083. doi: 10.1016/0019-2791(71)90496-4. [DOI] [PubMed] [Google Scholar]
- Fithian E., Kung P., Goldstein G., Rubenfeld M., Fenoglio C., Edelson R. Reactivity of Langerhans cells with hybridoma antibody. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2541–2544. doi: 10.1073/pnas.78.4.2541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geuze H. J., Slot J. W., Strous G. J., Peppard J., von Figura K., Hasilik A., Schwartz A. L. Intracellular receptor sorting during endocytosis: comparative immunoelectron microscopy of multiple receptors in rat liver. Cell. 1984 May;37(1):195–204. doi: 10.1016/0092-8674(84)90315-5. [DOI] [PubMed] [Google Scholar]
- Goldstein J. L., Brown M. S., Anderson R. G., Russell D. W., Schneider W. J. Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annu Rev Cell Biol. 1985;1:1–39. doi: 10.1146/annurev.cb.01.110185.000245. [DOI] [PubMed] [Google Scholar]
- Hanau D., Fabre M., Lepoittevin J. P., Stampf J. L., Grosshans E., Benezra C. La formation des granules de Langerhans semble liée à l'activité ATPasique membranaire des cellules de Langerhans épidermiques. C R Acad Sci III. 1985;301(5):167–172. [PubMed] [Google Scholar]
- Hanau D., Fabre M., Stampf J. L., Grosshans E., Benezra C. ATPase Langerhans cell staining: a technique allowing progression from light to electron microscope observation. J Invest Dermatol. 1986 Jan;86(1):5–8. doi: 10.1111/1523-1747.ep12283685. [DOI] [PubMed] [Google Scholar]
- Hanau D., Stampf J. L., Fabre M., Grosshans E., Benezra C. Induction of tolerance to urushiol by epicutaneous application of this hapten on dinitrofluorobenzene-treated skin. J Invest Dermatol. 1985 Jul;85(1):9–11. doi: 10.1111/1523-1747.ep12274489. [DOI] [PubMed] [Google Scholar]
- Harford J., Wolkoff A. W., Ashwell G., Klausner R. D. Monensin inhibits intracellular dissociation of asialoglycoproteins from their receptor. J Cell Biol. 1983 Jun;96(6):1824–1828. doi: 10.1083/jcb.96.6.1824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klareskog L., Tjernlund U., Forsum U., Peterson P. A. Epidermal Langerhans cells express Ia antigens. Nature. 1977 Jul 21;268(5617):248–250. doi: 10.1038/268248a0. [DOI] [PubMed] [Google Scholar]
- Lerch P. G., van de Rijn M., Schrier P., Terhorst C. Biochemical comparison of the T6 antigen and HLA-A,B antigens. Hum Immunol. 1983 Jan;6(1):13–30. doi: 10.1016/0198-8859(83)90070-8. [DOI] [PubMed] [Google Scholar]
- Maxfield F. R., Schlessinger J., Shechter Y., Pastan I., Willingham M. C. Collection of insulin, EGF and alpha2-macroglobulin in the same patches on the surface of cultured fibroblasts and common internalization. Cell. 1978 Aug;14(4):805–810. doi: 10.1016/0092-8674(78)90336-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy G. F., Bhan A. K., Sato S., Harrist T. J., Mihm M. C., Jr Characterization of Langerhans cells by the use of monoclonal antibodies. Lab Invest. 1981 Nov;45(5):465–468. [PubMed] [Google Scholar]
- Neppert J., Mueller-Eckhardt C. Monoclonal mouse antibodies to human MHC class I antigens cocap class II antigens. Tissue Antigens. 1984 Sep;24(3):187–189. doi: 10.1111/j.1399-0039.1984.tb02125.x. [DOI] [PubMed] [Google Scholar]
- Oka D., Nakagawa S., Ueki H., Kumon H., Ohmori H. Antigen in contact sensitivity: II. Scanning immunoelectron microscopic studies of the distribution of DNP groups on the epidermal cells of guinea pigs following skin painting with DNCB. J Dermatol. 1984 Feb;11(1):15–19. doi: 10.1111/j.1346-8138.1984.tb01434.x. [DOI] [PubMed] [Google Scholar]
- Rowden G., Lewis M. G., Sullivan A. K. Ia antigen expression on human epidermal Langerhans cells. Nature. 1977 Jul 21;268(5617):247–248. doi: 10.1038/268247a0. [DOI] [PubMed] [Google Scholar]
- Rowden G., Phillips T. M., Lewis M. G. Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscopic studies of surface antigens. Br J Dermatol. 1979 May;100(5):531–542. doi: 10.1111/j.1365-2133.1979.tb05578.x. [DOI] [PubMed] [Google Scholar]
- Schmitt D., Faure M., Dezutter-Dambuyant C., Tuffery D. Ultrastructural immunogold labelling of human Langerhans cells enriched epidermal cell suspension. Arch Dermatol Res. 1984;276(1):27–32. doi: 10.1007/BF00412558. [DOI] [PubMed] [Google Scholar]
- Shevach E. M., Rosenthal A. S. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med. 1973 Nov 1;138(5):1213–1229. doi: 10.1084/jem.138.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stingl G., Wolff-Schreiner E. C., Pichler W. J., Gschnait F., Knapp W., Wolff K. Epidermal Langerhans cells bear Fc and C3 receptors. Nature. 1977 Jul 21;268(5617):245–246. doi: 10.1038/268245a0. [DOI] [PubMed] [Google Scholar]
- Takezaki S., Morrison S. L., Berger C. L., Goldstein G., Chu A. C., Edelson R. L. Biochemical characterization of a differentiation antigen shared by human epidermal langerhans cells and cortical thymocytes. J Clin Immunol. 1982 Jul;2(3 Suppl):128S–134S. [PubMed] [Google Scholar]
- Terhorst C., van Agthoven A., LeClair K., Snow P., Reinherz E., Schlossman S. Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10. Cell. 1981 Mar;23(3):771–780. doi: 10.1016/0092-8674(81)90441-4. [DOI] [PubMed] [Google Scholar]
- Tse D. B., Cantor C. R., McDowell J., Pernis B. Recycling class I MHC antigens: dynamics of internalization, acidification, and ligand-degradation in murine T lymphoblasts. J Mol Cell Immunol. 1986;2(6):315–329. [PubMed] [Google Scholar]
- Via D. P., Willingham M. C., Pastan I., Gotto A. M., Jr, Smith L. C. Co-clustering and internalization of low-density lipoproteins and alpha 2-macroglobulin in human skin fibroblasts. Exp Cell Res. 1982 Sep;141(1):15–22. doi: 10.1016/0014-4827(82)90062-3. [DOI] [PubMed] [Google Scholar]
- Wang B. L., Scopsi L., Hartvig Nielsen M., Larsson L. I. Simplified purification and testing of colloidal gold probes. Histochemistry. 1985;83(2):109–115. doi: 10.1007/BF00495139. [DOI] [PubMed] [Google Scholar]
- Willingham M. C., Pastan I. H., Sahagian G. G., Jourdian G. W., Neufeld E. F. Morphologic study of the internalization of a lysosomal enzyme by the mannose 6-phosphate receptor in cultured Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6967–6971. doi: 10.1073/pnas.78.11.6967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolff K., Stingl G. The Langerhans cell. J Invest Dermatol. 1983 Jun;80 (Suppl):17s–21s. [PubMed] [Google Scholar]
- Woof J. M., Partridge L. J., Jefferis R., Burton D. R. Localisation of the monocyte-binding region on human immunoglobulin G. Mol Immunol. 1986 Mar;23(3):319–330. doi: 10.1016/0161-5890(86)90059-3. [DOI] [PubMed] [Google Scholar]
- Yonish-Rouach E., Schmitt D., Viac J., Knowles R., Cordier G., Brochier J. Monoclonal anti thymic cell antibodies detecting epidermal cells. Thymus. 1984;6(1-2):67–78. [PubMed] [Google Scholar]
- Ziegler H. K., Unanue E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):175–178. doi: 10.1073/pnas.79.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziegler K., Unanue E. R. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. J Immunol. 1981 Nov;127(5):1869–1875. [PubMed] [Google Scholar]
- van de Rijn M., Lerch P. G., Bronstein B. R., Knowles R. W., Bhan A. K., Terhorst C. Human cutaneous dendritic cells express two glycoproteins T6 and M241 which are biochemically identical to those found on cortical thymocytes. Hum Immunol. 1984 Apr;9(4):201–210. doi: 10.1016/0198-8859(84)90025-9. [DOI] [PubMed] [Google Scholar]
- van de Rijn M., Lerch P. G., Knowles R. W., Terhorst C. The thymic differentiation markers T6 and M241 are two unusual MHC class I antigens. J Immunol. 1983 Aug;131(2):851–855. [PubMed] [Google Scholar]