The processing routes determined by negatively charged residues in DR1-restricted T cell determinants

Détails

ID Serval
serval:BIB_B93068FB201C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The processing routes determined by negatively charged residues in DR1-restricted T cell determinants
Périodique
Journal of Immunology
Auteur(s)
Robadey  C., Ammerlaan  W., Muller  C., Cloutier  I., Sekaly  R. P., Haefliger  J. A., Demotz  S.
ISSN
0022-1767 (Print)
Statut éditorial
Publié
Date de publication
10/1997
Volume
159
Numéro
7
Pages
3238-46
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct 1
Résumé
The presentation pathways followed by DR1-restricted determinants from the fusion protein of measles virus were studied. By assessing the capacity of various APC preparations to stimulate fusion protein-specific T cells, it was shown that the determinant contained within the fusion protein sequence 254-268 (F254) relies on newly synthesized DR1 protein for its presentation. By contrast, the determinant contained within the fusion protein sequence 314-328 (F314) is captured by DR1 protein recycled from the plasma membrane. In vitro binding analyses showed that the F254 and F314 peptides optimally bind to DR1 at pH 4 and pH 5, respectively. In addition, it was found that binding of the F254 peptide to DR1 is much poorer at pH 7 than at pH 4, while binding of the F314 peptide was decreased only moderately at pH 7 as compared with pH 5. Substitution of the glutamic acid 261 for an alanine in the F254 peptide resulted in an analogue with an improved capacity of binding to DR1 at neutral pH. By contrast, replacement of the valine 319 by a glutamic acid in the F314 peptide generated an analogue with a decreased binding capacity at pH 7. These findings indicated that determinants that do not bear acidic residues are captured efficiently by DR1 molecules over a broader range of pH than determinants containing acidic residues. Binding analyses between DR1 and four additional peptides further supported this conclusion. Altogether, these results suggested that acidic residues, by tuning the optimal pH for the assembly of peptide-DR1 complexes, determine the processing pathway followed by the determinants.
Mots-clé
Amino Acid Sequence *Antigen Presentation Cell Line Epitopes, T-Lymphocyte/chemistry/immunology/*metabolism Glutamic Acid/metabolism/physiology HLA-DR Antigens/chemistry/*metabolism Humans Hydrogen-Ion Concentration Measles virus/genetics/immunology Molecular Sequence Data Peptide Fragments/immunology/metabolism Protein Binding/immunology Viral Fusion Proteins/immunology/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 14:47
Dernière modification de la notice
20/08/2019 16:27
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