Relationship between kinetic stability and immunogenicity of HLA‐DR4/peptide complexes

Immunodominant T cell epitopes from the autoantigen human cartilage glycoprotein 39 have previously been mapped in the context of HLA‐DR*0401 and *0402, using mice expressing HLA‐DR4 transgenes. We measured the dissociation rates of these epitopes from soluble recombinant DR*0401 and DR*0402 to asse...

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Bibliographic Details
Published in:European journal of immunology 2002-03, Vol.32 (3), p.662-670
Main Authors: Hall, Frances C., Rabinowitz, Joshua D., Busch, Robert, Visconti, Kevin C., Belmares, Michael, Patil, Namrata S., Cope, Andrew P., Patel, Salil, McConnell, Harden M., Mellins, Elizabeth D., Sonderstrup, Grete
Format: Article
Language:English
Subjects:
Adipokines
Amino Acid Sequence
Animals
Antigen presentation
Antigen Presentation - immunology
Antigen/peptide/epitope
Antigens - chemistry
Antigens - immunology
Cell Membrane - immunology
Cells, Cultured
Chitinase-3-Like Protein 1
DNA, Complementary - genetics
Drosophila melanogaster - cytology
Endosomes - chemistry
Endosomes - immunology
Glycoproteins - chemistry
Glycoproteins - immunology
histocompatibility antigen HLA
HLA-D Antigens - immunology
HLA-DR4 Antigen - chemistry
HLA-DR4 Antigen - immunology
Humans
Hybridomas - immunology
Hydrogen-Ion Concentration
Immunization
Immunodominant Epitopes - chemistry
Immunodominant Epitopes - immunology
Kinetics
Lectins
Macromolecular Substances
MHC
Mice
Mice, Transgenic
Molecular Sequence Data
Peptide Fragments - chemistry
Peptide Fragments - immunology
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - immunology
Structure-Activity Relationship
T lymphocyte
T-Lymphocytes - immunology
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Summary:Immunodominant T cell epitopes from the autoantigen human cartilage glycoprotein 39 have previously been mapped in the context of HLA‐DR*0401 and *0402, using mice expressing HLA‐DR4 transgenes. We measured the dissociation rates of these epitopes from soluble recombinant DR*0401 and DR*0402 to assess the relationship between peptide/HLA‐DR4 kinetic stability and immunogenicity. Experiments were performed at endosomal pH (5.5) and at cell surface pH (7), in the absence and presence of soluble recombinant HLA‐DM (sDM). All (4/4) immunodominant peptide/HLA‐DR complexes exhibit dissociation half‐times of 1 h to several days. In contrast, most (3/4) non‐immunodominant complexes dissociate with half‐times
ISSN:0014-2980
1521-4141
DOI:10.1002/1521-4141(200203)32:3<662::AID-IMMU662>3.0.CO;2-5