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

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2020 Mar 14

PMID 32164343

Citations 14

Authors

Zelia Silva

Tiago Ferro

Danielle Almeida

Helena Soares

Jose Alexandre Ferreira

Fanny M Deschepper

Paul J Hensbergen

Martina Pirro

Sandra J van Vliet

Sebastian Springer

Paula A Videira

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Targeting caspase-8: a new strategy for combating hepatocellular carcinoma.

Chen H, Lin Y, Chen J, Luo X, Kan Y, He Y Front Immunol. 2024; 15:1501659.

PMID: 39726605 PMC: 11669555. DOI: 10.3389/fimmu.2024.1501659.

New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells.

Silva Z, Rabaca J, Luz V, Lourenco R, Salio M, Oliveira A Cancer Immunol Immunother. 2024; 74(1):9.

PMID: 39487861 PMC: 11531459. DOI: 10.1007/s00262-024-03863-7.

Revisiting the immunopathology of congenital disorders of glycosylation: an updated review.

Pascoal C, Francisco R, Mexia P, Pereira B, Granjo P, Coelho H Front Immunol. 2024; 15:1350101.

PMID: 38550576 PMC: 10972870. DOI: 10.3389/fimmu.2024.1350101.

Sialic acid in the regulation of blood cell production, differentiation and turnover.

Irons E, Gc S, Lau J Immunology. 2024; 172(4):517-532.

PMID: 38503445 PMC: 11223974. DOI: 10.1111/imm.13780.

The role of N-glycosylation modification in the pathogenesis of liver cancer.

Hu M, Zhang R, Yang J, Zhao C, Liu W, Huang Y Cell Death Dis. 2023; 14(3):222.

PMID: 36990999 PMC: 10060418. DOI: 10.1038/s41419-023-05733-z.

References

Carrascal M, Severino P, Cabral M, Silva M, Ferreira J, Calais F . Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells. Mol Oncol. 2014; 8(3):753-65. PMC: 5528624. DOI: 10.1016/j.molonc.2014.02.008. View

Skipper J, Gulden P, Hendrickson R, Harthun N, Caldwell J, Shabanowitz J . Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100. Int J Cancer. 1999; 82(5):669-77. DOI: 10.1002/(sici)1097-0215(19990827)82:5<669::aid-ijc9>3.0.co;2-#. View

Smith K, Lutz C . Peptide-dependent expression of HLA-B7 on antigen processing-deficient T2 cells. J Immunol. 1996; 156(10):3755-64. View

Matsui K, Boniface J, Reay P, Schild H, Fazekas de St Groth B, Davis M . Low affinity interaction of peptide-MHC complexes with T cell receptors. Science. 1991; 254(5039):1788-91. DOI: 10.1126/science.1763329. View

Barnstable C, Bodmer W, Brown G, Galfre G, Milstein C, Williams A . Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978; 14(1):9-20. DOI: 10.1016/0092-8674(78)90296-9. View

Amith S, Jayanth P, Franchuk S, Finlay T, Seyrantepe V, Beyaert R . Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. Cell Signal. 2009; 22(2):314-24. DOI: 10.1016/j.cellsig.2009.09.038. View

Cabral M, Piteira A, Silva Z, Ligeiro D, Brossmer R, Videira P . Human dendritic cells contain cell surface sialyltransferase activity. Immunol Lett. 2010; 131(1):89-96. DOI: 10.1016/j.imlet.2010.02.009. View

Stam N, Spits H, Ploegh H . Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol. 1986; 137(7):2299-306. View

Palucka K, Banchereau J . Dendritic cells: a link between innate and adaptive immunity. J Clin Immunol. 1999; 19(1):12-25. DOI: 10.1023/a:1020558317162. View

10.

Pirro M, Schoof E, van Vliet S, Rombouts Y, Stella A, de Ru A . Glycoproteomic Analysis of MGL-Binding Proteins on Acute T-Cell Leukemia Cells. J Proteome Res. 2018; 18(3):1125-1132. PMC: 6399673. DOI: 10.1021/acs.jproteome.8b00796. View

11.

Brodsky F, Bodmer W, Parham P . Characterization of a monoclonal anti-beta 2-microglobulin antibody and its use in the genetic and biochemical analysis of major histocompatibility antigens. Eur J Immunol. 1979; 9(7):536-45. DOI: 10.1002/eji.1830090709. View

12.

Brodsky F, Parham P, Barnstable C, Crumpton M, Bodmer W . Monoclonal antibodies for analysis of the HLA system. Immunol Rev. 1979; 47:3-61. DOI: 10.1111/j.1600-065x.1979.tb00288.x. View

13.

Chiu I, Davis D, Strominger J . Trafficking of spontaneously endocytosed MHC proteins. Proc Natl Acad Sci U S A. 1999; 96(24):13944-9. PMC: 24170. DOI: 10.1073/pnas.96.24.13944. View

14.

Hansen T, Lee D . Mechanism of class I assembly with beta 2 microglobulin and loading with peptide. Adv Immunol. 1997; 64:105-37. DOI: 10.1016/s0065-2776(08)60888-3. View

15.

Feng C, Zhang L, Almulki L, Faez S, Whitford M, Hafezi-Moghadam A . Endogenous PMN sialidase activity exposes activation epitope on CD11b/CD18 which enhances its binding interaction with ICAM-1. J Leukoc Biol. 2011; 90(2):313-21. PMC: 3133440. DOI: 10.1189/jlb.1210708. View

16.

Ferreira J, Daniel-da-Silva A, Alves R, Duarte D, Vieira I, Santos L . Synthesis and optimization of lectin functionalized nanoprobes for the selective recovery of glycoproteins from human body fluids. Anal Chem. 2011; 83(18):7035-43. DOI: 10.1021/ac200916j. View

17.

Hoppes R, Oostvogels R, Luimstra J, Wals K, Toebes M, Bies L . Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes. J Immunol. 2014; 193(10):4803-13. PMC: 4226423. DOI: 10.4049/jimmunol.1400800. View

18.

Cole K, Steckbeck J, Rowles J, Desrosiers R, Montelaro R . Removal of N-linked glycosylation sites in the V1 region of simian immunodeficiency virus gp120 results in redirection of B-cell responses to V3. J Virol. 2004; 78(3):1525-39. PMC: 321372. DOI: 10.1128/jvi.78.3.1525-1539.2004. View

19.

Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E . CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell. 1999; 99(1):23-33. DOI: 10.1016/s0092-8674(00)80059-8. View

20.

Azevedo R, Silva A, Reis C, Santos L, Ferreira J . In silico approaches for unveiling novel glycobiomarkers in cancer. J Proteomics. 2017; 171:95-106. DOI: 10.1016/j.jprot.2017.08.004. View