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Open AccessArticle

MHC Class I Stability is Modulated by Cell Surface Sialylation in Human Dendritic Cells

1
UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
2
CDG & Allies – PPAIN- Congenital Disorders of Glycosylation & Allies - Professionals and Patient Associations International Network, 2829-516 Caparica, Portugal
3
Human Immunobiology and Pathogenesis, CEDOC-Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal
4
Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal
5
Porto Comprehensive Cancer Center (P.ccc), 4200-072 Porto, Portugal
6
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
7
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, 1081 HzAmsterdam, The Netherlands
8
Department of Life Sciences and Chemistry, Jacobs University, 28759 Bremen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(3), 249; https://doi.org/10.3390/pharmaceutics12030249
Received: 15 January 2020 / Revised: 4 March 2020 / Accepted: 6 March 2020 / Published: 10 March 2020
(This article belongs to the Special Issue Dendritic Cell Vaccines)
Maturation of human Dendritic Cells (DCs) is characterized by increased expression of antigen presentation molecules, and overall decreased levels of sialic acid at cell surface. Here, we aimed to identify sialylated proteins at DC surface and comprehend their role and modulation. Mass spectrometry analysis of DC’s proteins, pulled down by a sialic acid binding lectin, identified molecules of the major human histocompatibility complex class I (MHC-I), known as human leucocyte antigen (HLA). After desialylation, DCs showed significantly higher reactivity with antibodies specific for properly folded MHC-I-β2-microglobulin complex and for β2-microglobulin but showed significant lower reactivity with an antibody specific for free MHC-I heavy chain. Similar results for antibody reactivities were observed for TAP2-deficient lymphoblastoid T2 cells, which express HLA-A*02:01. Using fluorescent peptide specifically fitting the groove of HLA-A*02:01, instead of antibody staining, also showed higher peptide binding on desialylated cells, confirming higher surface expression of MHC-I complex. A decay assay showed that desialylation doubled the half-life of MHC-I molecules at cell surface in both DCs and T2 cells. The biological impact of DC´s desialylation was evaluated in co-cultures with autologous T cells, showing higher number and earlier immunological synapses, and consequent significantly increased production of IFN-γ by T cells. In summary, sialic acid content modulates the expression and stability of complex MHC-I, which may account for the improved DC-T synapses. View Full-Text
Keywords: dendritic-cells; antigen-presentation; MHC-I; immunogenicity; T-cell response; cancer-vaccines dendritic-cells; antigen-presentation; MHC-I; immunogenicity; T-cell response; cancer-vaccines
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MDPI and ACS Style

Silva, Z.; Ferro, T.; Almeida, D.; Soares, H.; Ferreira, J.A.; Deschepper, F.M.; Hensbergen, P.J.; Pirro, M.; van Vliet, S.J.; Springer, S.; Videira, P.A. MHC Class I Stability is Modulated by Cell Surface Sialylation in Human Dendritic Cells. Pharmaceutics 2020, 12, 249.

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