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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
RIIb2 and Fc
RIII, respectively), in the selection of peptides for presentation to T lymphocytes. B lymphoma cells expressing recombinant Fc
RIIb2 or Fc
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
RIIb2 and Fc
RIII. In contrast, the 7 other epitopes were efficiently presented only when antigens were internalized through Fc
RIII, but not through Fc
RIIb2. The capacity to present these latter epitopes was transferred to a tail-less Fc
RIIb2 by addition of the Fc
RIII-associated
chain cytoplasmic tail. Mutation of a single leucine residue at position 35 of the
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.
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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