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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01264

Lipid antigen presentation by CD1b and CD1d in Lysosomal Storage disease patients

Catia Pereira1,  Begoña Pérez-Cabezas1,  Helena Ribeiro1, Luz Maia2,  Teresa Cardoso3, Ana F. Dias2, Olga Azevedo4, Fatima Ferreira3, Paula Garcia5, Esmeralda Rodrigues3, Paulo Chaves3, Esmeralda Martins6, Patricio Aguiar7, Mercè Pineda8, Yasmina Amraoui9,  Simona Fecarotta10, Elisa Leão-Teles3, Shenglou Deng11, Paul B. Savage11 and  Fatima Macedo1*
  • 1i3S, Instituto de Investigação e Inovação em Saúde, Portugal
  • 2Instituto de Biologia Molecular e Celular (IBMC), Portugal
  • 3Centro Hospitalar São João, Portugal
  • 4Hospital da Senhora da Oliveira Guimarães, Portugal
  • 5Hospital and University Center of Coimbra, Portugal
  • 6Centro Hospitalar do Porto, Portugal
  • 7Hospital de Santa Maria, Portugal
  • 8Pediatric Research, Hospital Sant Joan de Déu, Spain
  • 9University Medical Centre, Johannes Gutenberg University Mainz, Germany
  • 10Azienda Ospedaliera Universitaria Federico II, Italy
  • 11Brigham Young University, United States

The lysosome has a key role in the presentation of lipid antigens by CD1 molecules. While defects in lipid antigen presentation and in invariant Natural Killer T (iNKT) cell response were detected in several mouse models of lysosomal storage diseases (LSD), the impact of lysosomal engorgement in human lipid antigen presentation is poorly characterized. Here, we analyzed the capacity of monocyte-derived dendritic cells (Mo-DCs) from Fabry, Gaucher, Niemann Pick type C and Mucopolysaccharidosis type VI disease patients to present exogenous antigens to lipid-specific T cells. The CD1b- and CD1d-restricted presentation of lipid antigens, by Mo-DCs, revealed an ability of LSD patients to induce CD1-restricted T cell responses within the control range. Similarly, freshly isolated monocytes from Fabry and Gaucher disease patients had a normal ability to present α-Galactosylceramide (α-GalCer) antigen by CD1d. Gaucher disease patients’ monocytes had an increased capacity to present α-Gal-(1-2)-αGalCer, an antigen that needs internalization and processing to become antigenic. In summary, our results show that, contrarily to what was observed in mouse models of LSD, Fabry, Gaucher, Niemann Pick type C and Mucopolysaccharidosis type VI disease patients do not present a decreased capacity to present CD1d-restricted lipid antigens. The percentage of total iNKT cells in the peripheral blood of these patients is also similar to control individuals. In addition, we show that the presentation of exogenous lipids that directly bind CD1b, the human CD1 isoform with an intracellular trafficking to the lysosome, is normal in these patients.

Keywords: CD1b, CD1d molecule, NKT (natural killer T) cell, Lysosomal Storage Diseases, Lipid antigen presentation, iNKT

Received: 07 Nov 2018; Accepted: 17 May 2019.

Edited by:

Peter M. Van Endert, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Reviewed by:

Reinhard Obst, Ludwig Maximilian University of Munich, Germany
Luis Graca, Universidade de Lisboa, Portugal  

Copyright: © 2019 Pereira, Pérez-Cabezas, Ribeiro, Maia, Cardoso, Dias, Azevedo, Ferreira, Garcia, Rodrigues, Chaves, Martins, Aguiar, Pineda, Amraoui, Fecarotta, Leão-Teles, Deng, Savage and Macedo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Fatima Macedo, i3S, Instituto de Investigação e Inovação em Saúde, Porto, Portugal,