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Review

Relevance of glycans in the interaction between T lymphocyte and the antigen presenting cell

ORCID Icon, ORCID Icon, , ORCID Icon, ORCID Icon & ORCID Icon
Pages 274-288 | Received 16 Sep 2020, Accepted 29 Oct 2020, Published online: 18 Nov 2020

References

  • Grakoui A, Bromley SK, Sumen C, et al. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285(5425):221–227. Juldoi:10.1126/science.285.5425.221.
  • Dustin ML. The immunological synapse. Cancer Immunol Res. 2014;2(11):1023–1033. doi:10.1158/2326-6066.CIR-14-0161.
  • Monks CRF, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells (Reprinted from). Nature. 1998;395(6697):82–86. doi:10.1038/25764.
  • Freiberg BA, Kupfer H, Maslanik W, et al. Staging and resetting T cell activation in SMACs. Nat Immunol. 2002;3(10):911–917. doi:10.1038/ni836.
  • Apweiler R, Hermjakob H, Sharon N. On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database11Dedicated to Prof. Akira Kobata and Prof. Harry Schachter on the occasion of their 65th birthdays. Biochim Biophys Acta (BBA). 1999;1473(1):4–8.
  • Khoury GA, Baliban RC, Floudas CA. Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database. Sci Rep. 2011;1(90):srep00090.
  • Roth J, Zuber C, Park S, et al. Protein N-glycosylation, protein folding, and protein quality control. Mol Cells. 2010;30(6):497–506. doi:10.1007/s10059-010-0159-z.
  • Xu CC, Ng DTW. Glycosylation-directed quality control of protein folding. Nat Rev Mol Cell Biol. 2015;16(12):742–752. doi:10.1038/nrm4073.
  • Giovannone N, Antonopoulos A, Liang J, et al. Human B cell differentiation is characterized by progressive remodeling of O-linked glycans. Front Immunol. 2018;9:2857.
  • Toscano MA, Bianco GA, Ilarregui JM, et al. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol. 2007;8(8):825–834. doi:10.1038/ni1482.
  • Ferreira IG, Pucci M, Venturi G, Malagolini N, Chiricolo M, Dall'Olio F. Glycosylation as a main regulator of growth and death factor receptors signaling. Int J Mol Sci. 2018;19(2):580–08.
  • Bartolazzi A, Nocks A, Aruffo A, Spring F, Stamenkovic I. Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. J Cell Biol. 1996;132(6):1199–1208. doi:10.1083/jcb.132.6.1199.
  • Hang Q, Isaji T, Hou S, Wang Y, Fukuda T, Gu J. A key regulator of cell adhesion: identification and characterization of important N-glycosylation sites on integrin α5 for cell migration. Mol Cell Biol. 2017;37(9):16.
  • Daniels MA, Hogquist KA, Jameson SC. Sweet 'n' sour: the impact of differential glycosylation on T cell responses. Nat Immunol. 2002;3(10):903–910. doi:10.1038/ni1002-903.
  • Comelli EM, Head SR, Gilmartin T, et al. A focused microarray approach to functional glycomics: transcriptional regulation of the glycome. Glycobiology. 2006;16(2):117–131. doi:10.1093/glycob/cwj048.
  • Raman R, Raguram S, Venkataraman G, Paulson JC, Sasisekharan R. Glycomics: an integrated systems approach to structure-function relationships of glycans. Nat Methods. 2005;2(11):817–824. doi:10.1038/nmeth807.
  • Turnbull JE, Field RA. Emerging glycomics technologies. Nat Chem Biol. 2007;3(2):74–77. doi:10.1038/nchembio0207-74.
  • Patsos G, Hebbe-Viton V, San Martin R, Paraskeva C, Gallagher T, Corfield A. Action of a library of O-glycosylation inhibitors on the growth of human colorectal cancer cells in culture. Biochem Soc Trans. 2005;33(Pt 4):721–723. doi:10.1042/BST0330721.
  • Ong QX, Han WP, Yang XY. O-GlcNAc as an integrator of signaling pathways. Front Endocrinol (Lausanne). 2018;9:599.
  • Issad T, Lefebvre T. Editorial: O-GlcNAcylation: expanding the frontiers. Front Endocrinol (Lausanne). 2019;10:867. doi:10.3389/fendo.2019.00867.
  • Rakus JF, Mahal LK. New technologies for glycomic analysis: toward a systematic understanding of the glycome. Annu Rev Anal Chem (Palo Alto Calif). 2011;4:367–392. doi:10.1146/annurev-anchem-061010-113951.
  • Oswald DM, Cobb BA. Emerging glycobiology tools: a renaissance in accessibility. Cell Immunol. 2018;333:2–8. doi:10.1016/j.cellimm.2018.04.010.
  • Riley NM, Bertozzi CR, Pitteri SJ. A pragmatic guide to enrichment strategies for mass spectrometry-based glycoproteomics. Mol Cell Proteomics. 2020;mcp.R120.002277. doi:10.1074/mcp.R120.002277.
  • Prescher JA, Bertozzi CR. Chemical technologies for probing glycans. Cell. 2006;126(5):851–854. doi:10.1016/j.cell.2006.08.017.
  • Agard NJ, Bertozzi CR. Chemical approaches to perturb, profile, and perceive glycans. Acc Chem Res. 2009;42(6):788–797. doi:10.1021/ar800267j.
  • Gray MA, Stanczak MA, Mantuano NR, et al. Targeted glycan degradation potentiates the anticancer immune response in vivo. Nat Chem Biol. 2020. doi:10.1038/s41589-020-0622-x.
  • Cummings RD, Pierce JM. The challenge and promise of glycomics. Chem Biol. 2014;21(1):1–15. doi:10.1016/j.chembiol.2013.12.010.
  • Kuball J, Hauptrock B, Malina V, et al. Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain. J Exp Med. 2009;206(2):463–475. doi:10.1084/jem.20082487.
  • Zhang K, Demarest SJ, Wu X, Fitchett JR. Glycosylation Profiling of α/β T Cell Receptor Constant Domains Expressed in Mammalian Cells. New York: Springer; 2017; p. 197–213.
  • Rudd PM, Wormald MR, Stanfield RL, et al. Roles for glycosylation of cell surface receptors involved in cellular immune recognition. J Mol Biol. 1999;293(2):351–366. doi:10.1006/jmbi.1999.3104.
  • Viola A, Lanzavecchia A. T cell activation determined by T cell receptor number and tunable thresholds. Science. 1996;273(5271):104–106.
  • Valitutti S, Lanzavecchia A. Serial triggering of TCRs: a basis for the sensitivity and specificity of antigen recognition. Immunol Today. 1997;18(6):299–304.
  • Demetriou M, Granovsky M, Quaggin S, Dennis JW. Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature. 2001;409(6821):733–739. doi:10.1038/35055582.
  • Dias AM, Dourado J, Lago P, et al. Dysregulation of T cell receptor N-glycosylation: a molecular mechanism involved in ulcerative colitis. Hum Mol Genet. 2014;23(9):2416–2427. doi:10.1093/hmg/ddt632.
  • Fujii H, Shinzaki S, Iijima H, et al. Core fucosylation on T Cells, required for activation of T-cell receptor signaling and induction of colitis in mice, is increased in patients with inflammatory bowel disease. Gastroenterology. 2016;150(7):1620–1632. doi:10.1053/j.gastro.2016.03.002.
  • Verhelst X, Dias AM, Colombel JF, et al. Protein glycosylation as a diagnostic and prognostic marker of chronic inflammatory gastrointestinal and liver diseases. Gastroenterology. 2020;158(1):95–110. doi:10.1053/j.gastro.2019.08.060.
  • Wang Y-N, Lee H-H, Hsu JL, Yu D, Hung M-C. The impact of PD-L1N-linked glycosylation on cancer therapy and clinical diagnosis. J Biomed Sci. 2020;27(1):77. doi:10.1186/s12929-020-00670-x.
  • Schumacher TNM. T-cell-receptor gene therapy. Nat Rev Immunol. 2002;2(7):512–519. doi:10.1038/nri841.
  • Liddy N, Bossi G, Adams KJ, et al. Monoclonal TCR-redirected tumor cell killing. Nat Med. 2012;18(6):980–987. doi:10.1038/nm.2764.
  • Swamy M, Dopfer EP, Molnar E, Alarcón B, Schamel WWA. The 450 kDa TCR Complex has a Stoichiometry of alphabetagammaepsilondeltaepsilonzetazeta. Scand J Immunol. 2008;67(4):418–420. doi:10.1111/j.1365-3083.2008.02082.x.
  • Samelson LE, Patel MD, Weissman AM, Harford JB, Klausner RD. Antigen activation of murine T cells induces tyrosine phosphorylation of a polypeptide associated with the T cell antigen receptor. Cell. 1986;46(7):1083–1090.
  • Sussman JJ, Bonifacino JS, Lippincott SJ, et al. Failure to synthesize the T Cell CD3-ζ chain: structure and function of a partial T cell receptor complex. Cell. 1988;52(1):85–95.
  • Weissman AM, Hou D, Orloff DG, et al. Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex. Proc Natl Acad Sci U S A. 1988;85(24):9709–9713. doi:10.1073/pnas.85.24.9709.
  • Borst J, Prendiville MA, Terhorst C. The T3 complex on human thymus-derived lymphocytes contains two different subunits of 20 kDa. Eur J Immunol. 1983;13(7):576–580. doi:10.1002/eji.1830130712.
  • Gold DP, Puck JM, Pettey CL, et al. Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex. Nature. 1986;321(6068):431–434. doi:10.1038/321431a0.
  • Clevers H, Alarcon B, Wileman T, Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6(1):629–662. doi:10.1146/annurev.iy.06.040188.003213.
  • Dietrich J, Neisig A, Hou X, Wegener AM, Gajhede M, Geisler C. Role of CD3 gamma in T cell receptor assembly. J Cell Biol. 1996;132(3):299–310. doi:10.1083/jcb.132.3.299.
  • Arnett KL, Harrison SC, Wiley DC. Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment. Proc Natl Acad Sci U S A. 2004;101(46):16268–16273. doi:10.1073/pnas.0407359101.
  • Manolios N, Bonifacino J, Klausner R. Transmembrane helical interactions and the assembly of the T cell receptor complex. Science. 1990;249(4966):274–277. doi:10.1126/science.2142801.
  • Zapata DA, Schamel WWA, Torres PS, et al. Biochemical differences in the alphabeta T cell receptor.CD3 surface complex between CD8+ and CD4+ human mature T lymphocytes. J Biol Chem. 2004;279(23):24485–24492. doi:10.1074/jbc.M311455200.
  • Rossi NE, Reine J, Pineda-Lezamit M, et al. Differential antibody binding to the surface alphabetaTCR.CD3 complex of CD4+ and CD8+ T lymphocytes is conserved in mammals and associated with differential glycosylation. Int Immunol. 2008;20(10):1247–1258. doi:10.1093/intimm/dxn081.
  • van de Griend RJ, Borst J, Tax WJ, Bolhuis RL. Functional reactivity of WT31 monoclonal antibody with T cell receptor-gamma expressing CD3 + 4-8- T cells. J Immunol. 1988;140(4):1107–1110.
  • C Chilson OP, Kelly-Chilson AE. Mitogenic lectins bind to the antigen receptor on human lymphocytes. Eur J Immunol. 1989;19(2):389–396. doi:10.1002/eji.1830190225.
  • Dither-Centerlind M-L, Axelsson B, Hammarstrom S, Hellström U, Perlmann P. Interaction of lectins with human T lymphocytes mitogenic properties, inhibitory effects, binding to the cell membrane and to isolated surface glycopeptides. Eur J Immunol. 1980;10(6):434–442.
  • Chilson OP, Boylston AW, Crumpton MJ. Phaseolus vulgaris phytohaemagglutinin (PHA) binds to the human T lymphocyte antigen receptor. EMBO J. 1984;3(13):3239–3245.
  • Kay JE. Mechanisms of T lymphocyte activation. Immunol Lett. 1991;29(1-2):51–54.
  • Pang B, Shin DH, Park KS, et al. Differential pathways for calcium influx activated by concanavalin A and CD3 stimulation in Jurkat T cells. Pflugers Arch - Eur J Physiol. 2012;463(2):309–318.
  • Riley JL, Mao M, Kobayashi S, et al. Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc Natl Acad Sci U S A. 2002;99(18):11790–11795. doi:10.1073/pnas.162359999.
  • Viola A, Schroeder S, Sakakibara Y, Lanzavecchia A. T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science. 1999;283(5402):680–682. doi:10.1126/science.283.5402.680.
  • Evans EJ, Esnouf RM, Manso-Sancho R, et al. Crystal structure of a soluble CD28-Fab complex. Nat Immunol. 2005;6(3):271–279. doi:10.1038/ni1170.
  • Aruffo A, Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987;84(23):8573–8577. doi:10.1073/pnas.84.23.8573.
  • Hanawa H, Ma Y, Mikolajczak SA, et al. A novel costimulatory signaling in human T lymphocytes by a splice variant of CD28. Blood. 2002;99(6):2138–2145. doi:10.1182/blood.v99.6.2138.
  • Wollscheid B, Bausch-Fluck D, Henderson C, et al. Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009;27(4):378–386. doi:10.1038/nbt.1532.
  • Ma BY, Mikolajczak SA, Yoshida T, Yoshida R, Kelvin DJ, Ochi A. CD28 T cell costimulatory receptor function is negatively regulated by N-linked carbohydrates. Biochem Biophys Res Commun. 2004;317(1):60–67. doi:10.1016/j.bbrc.2004.03.012.
  • Arenas-Del Ángel M, Legorreta-Herrera M, Mendoza-Hernández G, et al. Amaranthus leucocarpus lectin recognizes a moesin-like O-glycoprotein and costimulates murine CD3-activated CD4(+) T cells. Immun Inflamm Dis. 2015;3(3):182–195. doi:10.1002/iid3.58.
  • Recny MA, Luther MA, Knoppers MH, et al. N-Glycosylation is required for human cd2 immunoadhesion functions. J Biol Chem. 1992;267(31):22428–22434.
  • Wang J-h, Reinherz EL. Structural basis of cell–cell interactions in the immune system. Curr Opin Struct Biol. 2000;10(6):656–661.
  • Chang H-C, Tan K, Ouyang J, et al. Structural and Mutational Analyses of a CD8αβ Heterodimer and Comparison with the CD8αα Homodimer. Immunity. 2005;23(6):661–671.
  • Classon BJ, Brown Mh Fau - Garnett D, Garnett D, Fau - Somoza C, et al. The hinge region of the CD8 alpha chain: structure, antigenicity, and utility in expression of immunoglobulin superfamily domains. Int Immunol. 1992;4(2):215–25. doi:10.1093/intimm/4.2.215.
  • Merry AH, Gilbert RJC, Shore DA, et al. O-glycan sialylation and the structure of the stalk-like region of the T cell co-receptor CD8. J Biol Chem. 2003;278(29):27119–27128. doi:10.1074/jbc.M213056200.
  • Moody AM, North SJ, Reinhold B, et al. Sialic acid capping of CD8beta core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction. J Biol Chem. 2003;278(9):7240–7246. doi:10.1074/jbc.M210468200.
  • Daniels MA, Devine L, Miller JD, et al. CD8 binding to MHC class I molecules is influenced by T cell maturation and glycosylation. Immunity. 2001;15(6):1051–1061.
  • Galvan M, Murali-Krishna K, Ming LL, Baum L, Ahmed R. Alterations in cell surface carbohydrates on T cells from virally infected mice can distinguish effector/memory CD8(+) T cells from naive cells. J Immunol. 1998;161(2):641–648.
  • Harrington LE, Galvan M, Baum LG, Altman JD, Ahmed R. Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. J Exp Med. 2000;191(7):1241–1246. doi:10.1084/jem.191.7.1241.
  • Shore DA, Wilson IA, Dwek RA, Rudd PM. Glycosylation and the function of the T cell co-receptor CD8. Glycobiol Med. 2005;564:71–84.
  • Carr SA, Hemling ME, Folena-Wasserman G, et al. Protein and carbohydrate structural-analysis of a recombinant soluble cd4 receptor by mass-spectrometry. J Biol Chem. 1989;264(35):21286–21295.
  • Spellman MW, Leonard CK, Basa LJ, Gelineo I, Vanhalbeek H. Carbohydrate structures of recombinant soluble human CD4 expressed in Chinese hamster ovary cells . Biochemistry. 1991;30(9):2395–2406. doi:10.1021/bi00223a015.
  • Konig R, Ashwell G, Hanover JA. Glycosylation of cd4 - tunicamycin inhibits surface expression. J Biol Chem. 1988;263(19):9502–9507.
  • Tifft CJ, Proia RL, Camerini-Otero RD. The folding and cell-surface expression of cd4 requires glycosylation. J Biol Chem. 1992;267(5):3268–3273.
  • Schmid K, Hediger MA, Brossmer R, et al. Amino-acid-sequence of human plasma galactoglycoprotein - identity with the extracellular region of cd43 (sialophorin. Proc Natl Acad Sci U S A. 1992;89(2):663–667.
  • Cyster JG, Shotton DM, Williams AF. The dimensions of the lymphocyte-t glycoprotein leukosialin and identification of linear protein epitopes that can be modified by glycosylation. Embo J. 1991;10(4):893–902.
  • Matsumoto M, Atarashi K, Umemoto E, et al. CD43 functions as a ligand for E-selectin on activated T cells. J Immunol. 2005;175(12):8042–8050. doi:10.4049/jimmunol.175.12.8042.
  • Barran P, Fellinger W, Warren CE, Dennis JW, Ziltener HJ. Modification of CD43 and other lymphocyte O-glycoproteins by core 2 N-acetylglucosaminyltransferase. Glycobiology. 1997;7(1):129–136. doi:10.1093/glycob/7.1.129.
  • Brockhausen I, Pamela S, O-GalNAc Glycans, et al. In: Varki A CR, Esko JD, editors., editor. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press: 2017.
  • Jones AT, Federsppiel B, Ellies LG. Characterization of the activation-associated isoform of CD43 on murine T lymphocytes. J Immunol. 1994;153(8):3426–3439.
  • Ellies LG, Jones AT, Williams MJ, Ziltener HJ. Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease. Glycobiology. 1994;4(6):885–893. doi:10.1093/glycob/4.6.885.
  • Manjunath N, Correa M, Ardman M, Ardman B. Negative regulation of t-cell adhesion and activation by cd43. Nature. 1995;377(6549):535–538. doi:10.1038/377535a0.
  • Thurman EC, Walker J, Jayaraman S, Manjunath N, Ardman B, Green JM. Regulation of in vitro and in vivo T cell activation by CD43. Int Immunol. 1998;10(5):691–701. doi:10.1093/intimm/10.5.691.
  • Ostberg JR, Barth RK, Frelinger JG. The Roman god Janus: a paradigm for the function of CD43. Immunol Today. 1998;19(12):546–550.
  • Delon J, Kaibuchi K, Germain RN. Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. Immunity. 2001;15(5):691–701. doi:10.1016/S1074-7613(01)00231-X.
  • Carlow DA, Corbel SY, Williams MJ, Ziltener HJ. IL-2, -4, and -15 differentially regulate O-glycan branching and P-selectin ligand formation in activated CD8 T cells. J Immunol. 2001;167(12):6841–6848.
  • Higgins EA, Siminovitch KA, Zhuang DL, Brockhausen I, Dennis JW. Aberrant o-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the wiskott-aldrich syndrome. J Biol Chem. 1991;266(10):6280–6290.
  • Khan S, Holding S, Dore PC, Sewell WAC. Abnormal O-glycosylation of CD43 may account for some features of Wiskott-Aldrich syndrome. Med Hypotheses. 2008;70(2):269–272.
  • Barbosa JA, Santos-Aguado J, Mentzer SJ, Strominger JL, Burakoff SJ, Biro PA. Site-directed mutagenesis of class I HLA genes. Role of glycosylation in surface expression and functional recognition. J Exp Med. 1987;166(5):1329–1350. doi:10.1084/jem.166.5.1329.
  • Barber LD, Patel TP, Percival L, Gumperz JE, Lanier LL, Phillips JH. Unusual uniformity of the N-linked oligosaccharides of HLA-A, -B, and -C glycoproteins. J Immunol. 1996;156(9):3275–3284.
  • Parham P, Alpert BN, Alpert B, Orr HT, Strominger JL. Carbohydrate moiety of HLA antigens. Antigenic properties and amino acid sequences around the site of glycosylation. J Biol Chem. 1977;252(21):7555–7567.
  • Ploegh HL, Orr HT, Strominger JL. Biosynthesis and cell-surface localization of nonglycosylated human histocompatibility antigens. J Immunol. 1981;126(1):270–275.
  • Parham P. Functions for MHC class I carbohydrates inside and outside the cell. Trends Biochem Sci. 1996;21(11):427–433.
  • Mandal TK, Mukhopadhyay C. Effect of glycosylation on structure and dynamics of MHC class I glycoprotein: A molecular dynamics study. Biopolymers. 2001;59(1):11–23.
  • Ishikawa S, Kowal C, Fau - Cole B, Cole B, Fau - Thomson C, et al. Replacement of N-glycosylation sites on the MHC class II E alpha chain. Effect on thymic selection and peripheral T cell activation. J Immunol. 1995;154(10):5023–5029.
  • Salomonsen J, Marston D, Avila D, et al. The properties of the single chicken MHC classical class II alpha chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules. Immunogenetics. 2003;55(9):605–614. doi:10.1007/s00251-003-0620-7.
  • Brown JH, Jardetzky TS, Gorga JC, et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993;364(6432):33–39. doi:10.1038/364033a0.
  • Cullen Se Fau - Kindle CS, Kindle Cs Fau - Shreffler DC, Shreffler Dc Fau - Cowing C, Cowing C. Differential glycosylation of murine B cell and spleen adherent cell Ia antigens. J Immunol. 1981;127(4):1478–1484.
  • Barrera C, Espejo R, Reyes VE. Differential glycosylation of MHC class II molecules on gastric epithelial cells: implications in local immune responses. Hum Immunol. 2002;63(5):384–393. doi:10.1016/s0198-8859(02)00386-5.
  • Ryan SO, Bonomo J, Fau - Zhao F, Zhao F, Fau - Cobb BA, Cobb BA. MHC II glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation. J Exp Med. 2011;208(5):1041–1053.
  • Wei BY, Buerstedde Jm Fau - Bell M, Bell M, Fau - Chase C, et al. Functional effects of N-linked oligosaccharides located on the external domain of murine class II molecules. J Immunol. 1991;146(7):2358–2366.
  • Nag B, Passmore D, Fau - Kendrick T, Kendrick T, Fau - Bhayani H, et al. N-linked oligosaccharides of murine major histocompatibility complex class II molecule. Role in antigenic peptide binding, T cell recognition, and clonal nonresponsiveness. J Biol Chem. 1992;267(31):22624–22629.
  • Rock KL, Reits E, Neefjes J. Present Yourself! By MHC Class I and MHC Class II Molecules. Trends Immunol. 2016;37(11):724–737. doi:10.1016/j.it.2016.08.010.
  • Nielsen M, Andreatta M, Peters B, Buus S. Immunoinformatics: predicting peptide–MHC binding. Annu Rev Biomed Data Sci. 2020;3(1):191–115. doi:10.1146/annurev-biodatasci-021920-100259.
  • Carbone FR, Gleeson PA. Carbohydrates and antigen recognition by T cells. Glycobiology. 1997;7(6):725–730. doi:10.1093/glycob/7.6.725-d.
  • Harding CV, Kihlberg J, Fau - Elofsson M, Elofsson M, Fau - Magnusson G, et al. Glycopeptides bind MHC molecules and elicit specific T cell responses. J Immunol. 1993;151(5):2419–2425.
  • Deck MB, Sjolin P, Unanue ER, Kihlberg J. MHC-restricted, glycopeptide-specific T cells show specificity for both carbohydrate and peptide residues. J Immunol. 1999;162(8):4740–4744.
  • GalliStampino L, Meinjohanns E, Frische K, et al. T-cell recognition of tumor-associated carbohydrates: The nature of the glycan moiety plays a decisive role in determining glycopeptide immunogenicity. Cancer Research. 1997;57(15):3214–3222.
  • Suzuki T, Seko A, Kitajima K, Inoue Y, Inoue S. Identification of peptide:N-glycanase activity in mammalian-derived cultured cells. Biochem Biophys Res Commun. 1993;194(3):1124–1130. doi:10.1006/bbrc.1993.1938.
  • Haurum JS, Høier IB, Arsequell G, et al. Presentation of cytosolic glycosylated peptides by human class I major histocompatibility complex molecules in vivo. J Exp Med. 1999;190(1):145–150. doi:10.1084/jem.190.1.145.
  • Werdelin O, Meldal M, Jensen T. Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells. Proc Natl Acad Sci U S A. 2002;99(15):9611–9613. doi:10.1073/pnas.152345899.
  • Ninkovic T, Hanisch FG. O-glycosylated human MUC1 repeats are processed in vitro by immunoproteasomes. J Immunol. 2007;179(4):2380–2388.
  • Doe B, Steimer KS, Walker CM. Induction of HIV-1 envelope (gp120)-specific cytotoxic T lymphocyte responses in mice by recombinant CHO cell-derived gp120 is enhanced by enzymatic removal of N-linked glycans. Eur J Immunol. 1994;24(10):2369–2376. doi:10.1002/eji.1830241017.
  • Li HL, Xu CF, Blais S, et al. Proximal glycans outside of the epitopes regulate the presentation of HIV-1 envelope gp120 helper epitopes. J Immunol. 2009;182(10):6369–6378. doi:10.4049/jimmunol.0804287.
  • Dzhambazov B, Nandakumar KS, Kihlberg J, Fugger L, Holmdahl R, Vestberg M. Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules. J Immunol. 2006;176(3):1525–1533. doi:10.4049/jimmunol.176.3.1525.
  • Palitzsch B, Gaidzik N, Stergiou N, et al. A synthetic glycopeptide vaccine for the induction of a monoclonal antibody that differentiates between normal and tumor mammary cells and enables the diagnosis of human pancreatic cancer. Angew Chem Int Ed. 2016;55(8):2894–2898. doi:10.1002/anie.201509935.
  • Issad T, Masson E, Fau - Pagesy P, Pagesy PO. GlcNAc modification, insulin signaling and diabetic complications. Diabetes Metab. 2010;36(6 Pt 1):423–435.
  • Banerjee PS, Lagerlöf O, Hart GW. Roles of O-GlcNAc in chronic diseases of aging. Mol Aspects Med. 2016;51:1–15. doi:10.1016/j.mam.2016.05.005.
  • Issad TO. [O-GlcNAc glycosylation and regulation of cell signaling]. Med Sci (Paris). 2010;26(8-9):753–759. doi:10.1051/medsci/2010268-9753.
  • Whelan SA, Hart GW. Proteomic approaches to analyze the dynamic relationships between nucleocytoplasmic protein glycosylation and phosphorylation. Circ Res. 2003;93(11):1047–1058. doi:10.1161/01.RES.0000103190.20260.37.
  • Butkinaree C, Park K, Hart GO, LinkedβN. O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. Biochim Biophys Acta. 2010;1800(2):96–106. doi:10.1016/j.bbagen.2009.07.018.
  • Torres CR, Hart GW. Topography and polypeptide distribution of terminal n-acetylglucosamine residues on the surfaces of intact lymphocytes - evidence for o-linked glcnac. J Biol Chem. 1984;259(5):3308–3317.
  • Woo CM, Lund PJ, Huang AC, Davis MM, Bertozzi CR, Pitteri SJ. Mapping and Quantification of Over 2000 O-linked Glycopeptides in Activated Human T Cells with Isotope-Targeted Glycoproteomics (Isotag). Mol Cell Proteomics. 2018;17(4):764–775. doi:10.1074/mcp.RA117.000261.
  • Macintyre AN, Gerriets VA, Nichols AG, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 2014;20(1):61–72. doi:10.1016/j.cmet.2014.05.004.
  • Swamy M, Pathak S, Grzes KM, et al. Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. Nat Immunol. 2016;17(6):712–720. doi:10.1038/ni.3439.
  • Machacek M, Slawson C, Fields PE. O-GlcNAc: a novel regulator of immunometabolism. J Bioenerg Biomembr. 2018;50(3):223–229. doi:10.1007/s10863-018-9744-1.
  • Smith-Garvin JE, Koretzky GA, Jordan MS. T Cell Activation. Annu Rev Immunol. 2009;27(1):591–619. doi:10.1146/annurev.immunol.021908.132706.
  • Trinidad JC, Barkan DT, Gulledge BF, et al. Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Mol Cell Proteomics. 2012;11(8):215–229. doi:10.1074/mcp.O112.018366.
  • Lund PJ, Elias JE, Davis MM. Global analysis of O-GlcNAc glycoproteins in activated human T cells. J Immunol. 2016;197(8):3086–3098. doi:10.4049/jimmunol.1502031.
  • O'Donnell N, Zachara NE, Hart GW, Marth JD. Ogt-dependent X-chromosome-linked protein glycosylation is a requisite modification in somatic cell function and embryo viability. Mol Cell Biol. 2004;24(4):1680–1690. doi:10.1128/mcb.24.4.1680-1690.2004.

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