TY - JOUR

T1 - pH dependence of MHC class I-restricted peptide presentation.

AU - Stryhn, A

AU - Pedersen, L O

AU - Romme, T

AU - Olsen, A C

AU - Nissen, Mogens Holst

AU - Thorpe, C J

AU - Buus, S

N1 - 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

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 8666787

VL - 156

SP - 4191

EP - 4197

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -