Acidosis increases MHC class II-restricted presentation of a protein endowed with a pH-dependent heparan sulfate-binding ability

The Journal of Immunology : Official Journal of the American Association of Immunologists
Delphine KnittelMichel Léonetti

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 wit...Continue Reading

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Citations

Aug 3, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeanne GalaineOlivier Adotévi
Sep 12, 2020·Molecular Pharmacology·Omid TavassolyIman Tavassoly
Feb 14, 2021·Communications Biology·Xiaoxiao ZhangDing Xu
Jul 3, 2021·International Journal of Molecular Sciences·Valeria De PasqualeLuigi Michele Pavone

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