Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169

Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells

PMCID: PMC2189287  PMID: 2522497

Abstract

The capacity of dendritic cells to present protein antigens has been studied with two MHC class II-restricted, myoglobin-specific, T cell clones. Spleen dendritic cells and cultured epidermal Langerhans cells (LC) presented native myoglobin weakly and often not at all. These same populations were powerful stimulators of allogeneic T cells in the primary MLR. Freshly isolated LC were in contrast very active in presenting proteins to T cell clones but were weak stimulators of the MLR. Both fresh and cultured LC could present specific peptide fragments of myoglobin to the clones. These results suggest that dendritic cells in nonlymphoid tissues like skin can act as sentinels for presenting antigens in situ, their accessory function developing in two phases. First antigens are captured and appropriately presented. Further handling of antigen then is downregulated while the cells acquire strong sensitizing activity for the growth and function of resting T lymphocytes. The potent MLR stimulating activity of cultured epidermal LC and lymphoid dendritic cells probably reflects prior handling of antigens leading to the formation of allogeneic MHC-peptide complexes.

Full Text

The Full Text of this article is available as a PDF (627.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Austyn J. M., Steinman R. M., Weinstein D. E., Granelli-Piperno A., Palladino M. A. Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation. J Exp Med. 1983 Apr 1;157(4):1101–1115. doi: 10.1084/jem.157.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  3. DeLisi C., Berzofsky J. A. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hanau D., Fabre M., Schmitt D. A., Garaud J. C., Pauly G., Tongio M. M., Mayer S., Cazenave J. P. Human epidermal Langerhans cells cointernalize by receptor-mediated endocytosis "nonclassical" major histocompatibility complex class I molecules (T6 antigens) and class II molecules (HLA-DR antigens). Proc Natl Acad Sci U S A. 1987 May;84(9):2901–2905. doi: 10.1073/pnas.84.9.2901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heufler C., Koch F., Schuler G. Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med. 1988 Feb 1;167(2):700–705. doi: 10.1084/jem.167.2.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Inaba K., Koide S., Steinman R. M. Properties of memory T lymphocytes isolated from the mixed leukocyte reaction. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7686–7690. doi: 10.1073/pnas.82.22.7686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Inaba K., Schuler G., Witmer M. D., Valinksy J., Atassi B., Steinman R. M. Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes. J Exp Med. 1986 Aug 1;164(2):605–613. doi: 10.1084/jem.164.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Inaba K., Steinman R. M., Van Voorhis W. C., Muramatsu S. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6041–6045. doi: 10.1073/pnas.80.19.6041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klinkert W. E., LaBadie J. H., Bowers W. E. Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues. J Exp Med. 1982 Jul 1;156(1):1–19. doi: 10.1084/jem.156.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Knight S. C., Balfour B. M., O'Brien J., Buttifant L., Sumerska T., Clarke J. Role of veiled cells in lymphocyte activation. Eur J Immunol. 1982 Dec;12(12):1057–1060. doi: 10.1002/eji.1830121214. [DOI] [PubMed] [Google Scholar]
  12. Livingstone A. M., Fathman C. G. The structure of T-cell epitopes. Annu Rev Immunol. 1987;5:477–501. doi: 10.1146/annurev.iy.05.040187.002401. [DOI] [PubMed] [Google Scholar]
  13. Macatonia S. E., Knight S. C., Edwards A. J., Griffiths S., Fryer P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med. 1987 Dec 1;166(6):1654–1667. doi: 10.1084/jem.166.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morel P. A., Livingstone A. M., Fathman C. G. Correlation of T cell receptor V beta gene family with MHC restriction. J Exp Med. 1987 Aug 1;166(2):583–588. doi: 10.1084/jem.166.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nussenzweig M. C., Steinman R. M. Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction. J Exp Med. 1980 May 1;151(5):1196–1212. doi: 10.1084/jem.151.5.1196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pugh C. W., MacPherson G. G., Steer H. W. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med. 1983 Jun 1;157(6):1758–1779. doi: 10.1084/jem.157.6.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Romani N., Inaba K., Puré E., Crowley M., Witmer-Pack M., Steinman R. M. A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes. J Exp Med. 1989 Mar 1;169(3):1153–1168. doi: 10.1084/jem.169.3.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schuler G., Auböck J., Linert J. Enrichment of epidermal Langerhans cells by immunoadsorption to Staphylococcus aureus cells. J Immunol. 1983 May;130(5):2008–2010. [PubMed] [Google Scholar]
  19. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974 Feb 1;139(2):380–397. doi: 10.1084/jem.139.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steinman R. M., Inaba K. Stimulation of the primary mixed leukocyte reaction. Crit Rev Immunol. 1985;5(4):331–348. [PubMed] [Google Scholar]
  23. Steinman R. M., Kaplan G., Witmer M. D., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med. 1979 Jan 1;149(1):1–16. doi: 10.1084/jem.149.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Steinman R. M., Witmer M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132–5136. doi: 10.1073/pnas.75.10.5132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Takigawa M., Iwatsuki K., Yamada M., Okamoto H., Imamura S. The Langerhans cell granule is an adsorptive endocytic organelle. J Invest Dermatol. 1985 Jul;85(1):12–15. doi: 10.1111/1523-1747.ep12274494. [DOI] [PubMed] [Google Scholar]
  26. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
  27. Witmer-Pack M. D., Olivier W., Valinsky J., Schuler G., Steinman R. M. Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med. 1987 Nov 1;166(5):1484–1498. doi: 10.1084/jem.166.5.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Witmer-Pack M. D., Valinsky J., Olivier W., Steinman R. M. Quantitation of surface antigens on cultured murine epidermal Langerhans cells: rapid and selective increase in the level of surface MHC products. J Invest Dermatol. 1988 Mar;90(3):387–394. doi: 10.1111/1523-1747.ep12456460. [DOI] [PubMed] [Google Scholar]
  29. Wolff K., Schreiner E. Uptake, intracellular transport and degradation of exogenous protein by Langerhans cells. An electron microscopic-cytochemical study using peroxidase as tracer substance. J Invest Dermatol. 1970 Jan;54(1):37–47. doi: 10.1111/1523-1747.ep12551501. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES