Invariant chain prevents the HLA-DR-restricted presentation of a cytosolic peptide.
Three properties of the HLA-DR-associated invariant chain (Ii) may contribute to the distinction between the class I and class II Ag presentation pathways. First, Ii prevents peptide binding to alpha beta 1 Ii complexes. Second, Ii promotes assembly of class II alpha beta heterodimers and their transport out of the endoplasmic reticulum. Third, Ii provides a targeting signal for the transport of class II molecules to endocytic compartments. However, it is not known whether Ii can prevent class II-restricted T cell recognition of endogenous peptides transported into the endoplasmic reticulum. In addition, recent evidence has indicated that, in the absence of Ii, newly synthesized class II molecules cannot form stable complexes with peptides. In this study, transfected human fibroblast cells expressing HLA-DR1 alone or with an excess of Ii were tested for their ability to present a DR1-restricted epitope of the influenza virus matrix protein produced as a short cytosolic peptide by use of an episomal expression vector. Presentation to a DR1-restricted T cell clone was very efficient in cells expressing class II molecules without Ii, but not in cells expressing class II and Ii. The inhibition by Ii was specific for the endogenous cytosolic peptide, because the same epitope processed from exogenous influenza virus particles was presented only by cells expressing class II with Ii. Ii did not inhibit the HLA-A2-restricted presentation of another cytosolic peptide. Thus, T cells can detect a cytosolic peptide loaded onto class II alpha beta heterodimers, and Ii prevents such endogenous peptide presentation.
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Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
LaVaute
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Pinet
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Jaraquemada
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D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte; D001483:Base Sequence; D003600:Cytosol / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011994:Recombinant Proteins
D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011994:Recombinant Proteins; C045084:invariant chain