pH dependence of MHC class I-restricted peptide presentation.
Research output: Contribution to journal › Journal article › Research › peer-review
The function of MHC class I molecules is to bind and present antigenic peptides to cytotoxic T cells. Here, we report that class I-restricted peptide presentation is strongly pH dependent. The presentation of some peptides was enhanced at acidic pH, whereas the presentation of others was inhibited. Biochemical peptide-MHC class I binding assays demonstrated that peptide-MHC class I complexes are more stable at neutral pH than at acidic pH. We suggest that acid-dependent peptide dissociation can generate empty class I molecules and that the resulting binding potential can be exploited by a subset of peptide-MHC class I combinations, in some cases leading to considerable peptide exchange. We further speculate that the relative instability of peptide-class I complexes under acidic conditions may affect the outcome of class I-restricted Ag presentation, as less stably associated peptides may dissociate from class I during passage of the acidic trans-Golgi network, and therefore may not be presented. Finally, our results may in part explain how endocytosed proteins can be presented by MHC class I molecules to cytotoxic T cells.
Original language | English |
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Journal | Journal of Immunology |
Volume | 156 |
Issue number | 11 |
Pages (from-to) | 4191-7 |
Number of pages | 6 |
ISSN | 0022-1767 |
Publication status | Published - 1996 |
Bibliographical note
Keywords: Amino Acid Sequence; Animals; Antigen Presentation; Histocompatibility Antigens Class I; Hybridomas; Hydrogen-Ion Concentration; Kinetics; Mice; Molecular Sequence Data; Peptides; Protein Binding; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured
ID: 8746588