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© The Rockefeller University Press, 0022-1007/1998/2/505/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 4, February 16, 1998 505-515


Articles

Type II and III Receptors for Immunoglobulin G (IgG) Control the Presentation of Different T Cell Epitopes from Single IgG-complexed Antigens

Sebastian Amigorena*, Danielle Lankar*, Volker Briken*, Laurent Gapin{ddagger}, Mireille Viguier§, and Christian Bonnerot*

From the * Institut National de la Santé et de la Recherche Médicale, Contrat Jeune Formation 95-01, Institut Curie, Section Recherche, 75005, Paris, France; and {ddagger} Biologie moléculaire de gène, Institut National de la Santé et de la Recherche Médicale U277, Institut Pasteur, 75015, Paris, France; and § Laboratoire d'immunologie des pathologies infectieuses et tumorales, Institut Cochin Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale U445, 75014, Paris, France

T cell receptors on CD4+ lymphocytes recognize antigen-derived peptides presented by major histocompatibility complex (MHC) class II molecules. A very limited set of peptides among those that may potentially bind MHC class II is actually presented to T lymphocytes. We here examine the role of two receptors mediating antigen internalization by antigen presenting cells, type IIb2 and type III receptors for IgG (Fc{gamma}RIIb2 and Fc{gamma}RIII, respectively), in the selection of peptides for presentation to T lymphocytes. B lymphoma cells expressing recombinant Fc{gamma}RIIb2 or Fc{gamma}RIII were used to assess the presentation of several epitopes from two different antigens. 4 out of the 11 epitopes tested were efficiently presented after antigen internalization through Fc{gamma}RIIb2 and Fc{gamma}RIII. In contrast, the 7 other epitopes were efficiently presented only when antigens were internalized through Fc{gamma}RIII, but not through Fc{gamma}RIIb2. The capacity to present these latter epitopes was transferred to a tail-less Fc{gamma}RIIb2 by addition of the Fc{gamma}RIII-associated {gamma} chain cytoplasmic tail. Mutation of a single leucine residue at position 35 of the {gamma} chain cytoplasmic tail resulted in the selective loss of presentation of these epitopes. Therefore, the nature of the receptor that mediates internalization determines the selection of epitopes presented to T lymphocytes within single protein antigens.


We are grateful to Drs. Ming-Zong Lai and Eli E. Sercarz for providing us with several anti-CI {lambda} repressor and anti-HEL T cell hybridomas, to P. Benaroch and G. Langsley for critically reading the manuscript and to all members of the CJF-INSERM 95-01 for useful discussions.

This work was supported by grants from the INSERM, Institut Curie, the Association de Recherche contre le Cancer (ARC), and the Ligue Nationale Contre le Cancer. L. Gapin was supported by ARC and Pasteur-Weizman fellowships and V. Briken by an E.C. fellowship.

Address correspondence to Sebastian Amigorena, INSERM CJF 95-01, Institut Curie, Section Recherche, 12 rue Lhomond, 75005, Paris, France. Phone: 33-01-42-34-63-89; Fax: 33-01-42-34-63-82; E-mail, s.amigorena{at}curie.fr

1 Abbreviations used in this paper: Ii, invariant chain; ITAM, immunoreceptor tyrosine kinase activation motif; HEL, hen egg lysozome; HRP, horseradish, peroxidase; PTK, protein tyrosine kinase.


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