Abstract
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 1h to several days. In contrast, most (3/4) non-immunodominant complexes dissociate with half-times <30 min under at least one of these conditions. Interestingly, a complex which is stable except in the presence of HLA-DM at pH 5.5 is immunogenic only following peptide immunization, while a complex which is stable at acidic but not at neutral pH, is non-immunogenic following either whole protein or peptide immunization. These data indicate that kinetic stability of peptide/MHC complexes in vivo is a key determinant of immunogenicity.
| Original language | English |
|---|---|
| Pages (from-to) | 662-70 |
| Number of pages | 9 |
| Journal | Current protocols in immunology |
| Volume | 32 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2002 |
Keywords
- Adipokines
- Amino Acid Sequence
- Animals
- Antigen Presentation
- Antigens
- Cell Membrane
- Cells, Cultured
- Chitinase-3-Like Protein 1
- DNA, Complementary
- Drosophila melanogaster
- Endosomes
- Glycoproteins
- HLA-D Antigens
- HLA-DR4 Antigen
- Humans
- Hybridomas
- Hydrogen-Ion Concentration
- Immunization
- Immunodominant Epitopes
- Kinetics
- Lectins
- Macromolecular Substances
- Mice
- Mice, Transgenic
- Molecular Sequence Data
- Peptide Fragments
- Recombinant Fusion Proteins
- Structure-Activity Relationship
- T-Lymphocytes