Acidosis Increases MHC Class II-Restricted Presentation of a Protein Endowed with a pH-Dependent Heparan Sulfate-Binding Ability.

Abstract : Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed molecules that participate in numerous biological processes. We previously showed that HSPGs expressed on the surface of APCs can serve as receptors for a hybrid protein containing an HS ligand and an Ag, which leads to more efficient stimulation of Th cells. To investigate whether such behavior is shared by proteins with inherent HS-binding ability, we looked for proteins endowed with this characteristic. We found that diphtheria toxin and its nontoxic mutant, called CRM197, can interact with HS. However, we observed that their binding ability is higher at pH 6 than at pH 7.4. Therefore, as extracellular acidosis occurs during infection by various micro-organisms, we assessed whether HS-binding capacity affects MHC class II-restricted presentation at different pHs. We first observed that pH decrease allows CRM197 binding to HSPG-expressing cells, including APCs. Then, we showed that this interaction enhances Ag uptake and presentation to Th cells. Lastly, we observed that pH decrease does not affect processing and presentation abilities of the APCs. Our findings show that acidic pH causes an HSPG-mediated uptake and an enhancement of T cell stimulation of Ags with the inherent ability to bind HSPGs pH-dependently. Furthermore, they suggest that proteins from micro-organisms with this binding characteristic might be supported more efficiently by the adaptive immune system when acidosis is triggered during infection.
Type de document :
Article dans une revue
Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2015, 194 (8), pp.3601-11
Liste complète des métadonnées

http://hal.univ-grenoble-alpes.fr/hal-01149495
Contributeur : Frank Thomas <>
Soumis le : jeudi 7 mai 2015 - 11:01:39
Dernière modification le : mercredi 14 mars 2018 - 16:41:17

Identifiants

  • HAL Id : hal-01149495, version 1
  • PUBMED : 25754736

Citation

Delphine Knittel, Alexandra Savatier, Grégory Upert, Hugues Lortat-Jacob, Michel Léonetti. Acidosis Increases MHC Class II-Restricted Presentation of a Protein Endowed with a pH-Dependent Heparan Sulfate-Binding Ability.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2015, 194 (8), pp.3601-11. 〈hal-01149495〉

Partager

Métriques

Consultations de la notice

200