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J Exp Med. 1989 March 1; 169(3): 1169–1178.
PMCID: PMC2189287

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

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Steinman RM, Witmer MD. 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. [PubMed]
  • Nussenzweig MC, Steinman RM. Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction. J Exp Med. 1980 May 1;151(5):1196–1212. [PMC free article] [PubMed]
  • Klinkert WE, LaBadie JH, Bowers WE. Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues. J Exp Med. 1982 Jul 1;156(1):1–19. [PMC free article] [PubMed]
  • Knight SC, Balfour BM, 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. [PubMed]
  • Austyn JM, Steinman RM, Weinstein DE, Granelli-Piperno A, Palladino MA. Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation. J Exp Med. 1983 Apr 1;157(4):1101–1115. [PMC free article] [PubMed]
  • Pugh CW, MacPherson GG, Steer HW. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med. 1983 Jun 1;157(6):1758–1779. [PMC free article] [PubMed]
  • Schuler G, Steinman RM. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. [PMC free article] [PubMed]
  • Inaba K, Schuler G, Witmer MD, Valinksy J, Atassi B, Steinman RM. 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. [PMC free article] [PubMed]
  • Witmer-Pack MD, Olivier W, Valinsky J, Schuler G, Steinman RM. 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Morel PA, Livingstone AM, Fathman CG. Correlation of T cell receptor V beta gene family with MHC restriction. J Exp Med. 1987 Aug 1;166(2):583–588. [PMC free article] [PubMed]
  • Steinman RM, Kaplan G, Witmer MD, Cohn ZA. 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. [PMC free article] [PubMed]
  • Macatonia SE, Knight SC, Edwards AJ, 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. [PMC free article] [PubMed]
  • Romani N, Inaba K, Puré E, Crowley M, Witmer-Pack M, Steinman RM. 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. [PMC free article] [PubMed]
  • Unanue ER. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. [PubMed]
  • DeLisi C, Berzofsky JA. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. [PubMed]
  • Livingstone AM, Fathman CG. The structure of T-cell epitopes. Annu Rev Immunol. 1987;5:477–501. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. [PubMed]
  • Inaba K, Steinman RM. 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. [PMC free article] [PubMed]
  • Inaba K, Koide S, Steinman RM. Properties of memory T lymphocytes isolated from the mixed leukocyte reaction. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7686–7690. [PubMed]
  • Steinman RM, Cohn ZA. 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • 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]
  • 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. [PubMed]
  • Hanau D, Fabre M, Schmitt DA, Garaud JC, Pauly G, Tongio MM, Mayer S, Cazenave JP. 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. [PubMed]
  • Inaba K, Steinman RM, Van Voorhis WC, 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. [PubMed]
  • Steinman RM, Inaba K. Stimulation of the primary mixed leukocyte reaction. Crit Rev Immunol. 1985;5(4):331–348. [PubMed]
  • Witmer-Pack MD, Valinsky J, Olivier W, Steinman RM. 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. [PubMed]

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