Post-translational modifications of proteins: Implications for aging, antigen recognition, and autoimmunity

Biogerontology

Volumn 5, Issue 3, 2004, Pages 139-158

  Cloos, Paul A C ^a   Christgau, Stephan ^a  

^a NORDIC BIOSCIENCE A S   (Denmark)

Author keywords

Aging; Antigen presentation; Antigen processing; Citrullination; Deamidation; Glycation; Isoaspartyl formation; Oxidation; Post ranslational modifications

Indexed keywords

ANTIGEN; AUTOANTIGEN; ENZYME INHIBITOR; ORGANIC COMPOUND;

AGING; ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; ANTIGENICITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; DEAMINATION; DIAGNOSTIC PROCEDURE; GLYCATION; HUMAN; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; IMMUNOREACTIVITY; IMMUNOTHERAPY; ISOMERIZATION; PATHOGENESIS; PATHOLOGY; PHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN GLYCOSYLATION; PROTEIN INTERACTION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; RACEMIZATION; REVIEW; T LYMPHOCYTE;

AGING; ANTIGENS; AUTOIMMUNITY; GLYCOSYLATION; HUMANS; ISOMERISM; MAJOR HISTOCOMPATIBILITY COMPLEX; OXIDATIVE STRESS; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEINS; STEREOISOMERISM;

EID: 3442898781     PISSN: 13895729     EISSN: None     Source Type: Journal    
DOI: 10.1023/B:BGEN.0000031152.31352.8b     Document Type: Review

References (119)

1. Ahsan H, Ali A and Ali R (2003) Oxygen free radicals and systemic autoimmunity. Clin Exp Immunol 131: 398-404
2. Arentz-Hansen H, Korner R, Molberg O, Quarsten H, Vader W, Kooy YM, Lundin KE, Koning F, Roepstorff P, Sollid LM and McAdam SN (2000) The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated Gln targeted by tissue transglutaminase. J Exp Med 191: 603-612
3. Armbrecht HJ, Nemani RK and Wongsuwarat N (1993) Protein phosphorylation: changes with age and age-related diseases. J Am Geriatr Soc 41: 873-879
4. Asaga H, Yamada M and Senshu T (1998) Selective deimination of vimentin in calcium ionophore-induced apoptosis of mouse peritoneal macrophages. Biochem Biophys Res Commun 243: 641-646
5. Bäcklund J, Treschow A, Bockermann R, Holm B, Holm L, Issazadeh-Navikas S, Kihlberg J and Holmdahl R (2002) Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis. Eur J Immunol 32: 3776-3784
6. Bank RA, Bayliss MT, Lafeber FP, Maroudas A and Tekoppele JM (1998) Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage. Biochem J 330: 345-351
7. Bas S, Genevay S, Meyer O and Gabay C (2003) Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology (Oxford) 42: 677-680
8. Beniac DR, Wood DD, Palaniyar N, Ottensmeyer FP, Moscarello MA and Harauz G (2000) Cryoelectron microscopy of protein-lipid complexes of human myelin basic protein charge isomers differing in degree of citrullination. J Struct Biol 129: 80-95
9. Biagi F, Parnell ND, Thomas PD, Ellis HJ and Ciclitira PJ (1999) A new model for the pathogenesis of celiac disease. Gastroenterology 116: 1277-1278
10. Boggs JM, Rangaraj G, Koshy KM, Ackerley C, Wood DD and Moscarello MA (1999) Highly deiminated isoform of myelin basic protein from multiple sclerosis brain causes fragmentation of lipid vesicles. J Neurosci Res 57: 529-535
11. Brady GW, Fein DB, Wood DD and Moscarello MA (1985) The role of charge microheterogeneity of human myelin basic protein in the formation of phosphatidylglycerol multilayers. Biochem Biophys Res Commun 126: 1161-1165
12. Brange J, Langkjær L, Havelund S and Vølund A (1992) Chemical stability of insulin. 1. Hydrolytic degradation during storage of pharmaceutical preparations. Pharm Res 9: 715-726
13. Brennan TV, Anderson JW, Jia Z, Waygood EB and Clarke S (1994) Repair of spontaneously deamidated HPr phosphocarrier protein catalyzed by the L-isoaspartate-(D-aspartate) O-methyltransferase. J Biol Chem 269: 24586-24595
14. Buntinx M, Stinissen P, Steels P, Ameloot M and Raus J (2002) Immune-mediated oligodendrocyte injury in multiple sclerosis: molecular mechanisms and therapeutic interventions. Crit Rev Immunol 22: 391-424
15. Cao L, Sun D and Whitaker JN (1998) Citrullinated myelin basic protein induces experimental autoimmune encephalomyelitis in Lewis rats through a diverse T cell repertoire. J Neuroimmunol 88: 21-29
16. Casciola-Rosen LA, Anhalt G and Rosen A (1994) Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 179: 1317-1330
17. Chen JR, Takahashi M, Suzuki M, Kushida K, Miyamoto S and Inoue T (1998) Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis. J Rheumatol 25: 2440-2444
18. Chui D, Sellakumar G, Green RS, Sutton-Smith M, McQuinstan T, Marek KW, Morris HR, Dell A and Marth JD. (2001) Genetic remodeling of protein glycosylation in vivo induces autoimmune disease. Proc Natl Acad Sci USA 98: 1142-1147
19. Cloos PAC (2001) Prevention and alleviation of autoimmunity by modulating the activity of PIMT. PCT application
20. Cloos PAC and Christgau S (1999) Specific autoimmune reactions against isomerized/optically inverted epitopes: application for diagnosis of autoimmune diseases. PCT Application. WO 0113110
21. Cloos PAC and Christgau S (2002) Non-enzymatic covalent modifications of proteins: mechanisms, physiological consequences and clinical applications. Matrix Biology 21: 39-52
22. Cloos PAC and Jensen AL (2000) Age-related de-phosphorylation of proteins in dentin: a biological tool for assessment of protein age. Biogerontology 1: 341-356
23. Cloos PAC and Fledelius C (2000) Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential. Biochem J 345: 473-480
24. Corthay A, Backlund J, Broddefalk J, Michaelsson E, Goldschmidt TJ, Kihlberg J and Holmdahl R (1998) Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis. Eur J Immunol 28: 2580-2590
25. Dando PM et al. (1999) Pig kidney legumain: an asparaginyl endopeptidase with restricted specificity. Biochem J 339: 743-749.
26. Davies KJA (1987) Protein damage and degradation by oxygen radicals. I. General aspects. J Biol Chem 262: 9895-9901
27. Davies JL, Kawaguchi Y, Bennett ST, et al. (1994) A genomewide search for human type 1 diabetes susceptibility genes. Nature 371: 130-136
28. Delepine M, Pociot F, Habita C, et al. (1997) Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6. Am J Hum Genet 60: 174-187
29. Demetriou M, Granovsky M, Quaggin S and Dennis JW (2001) Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409: 733-739
30. DiPaolo RJ and Unanue ER (2001) The level of peptide-MHC complex determines the susceptibility to autoimmune diabetes: studies in HEL transgenic mice. Eur J Immunol 31: 3453-3459
31. Doyle HA and Mamula MJ (2001) Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol 22: 443-449
32. Doyle HA, Gee RJ and Mamula MJ (2003) A failure to repair self-proteins leads to T cell hyperproliferation and autoantibody production. J Immunol 171: 2840-2847
33. Ernst DN, Weigle WO and Hobbs MV (1993) Aging and lymphokine production by T cell subsets. Stem Cells. 11: 487-498
34. Farr SB and Kogoma T (1991) Oxidative stress responses in Escherichia coli and Salmonella typhimurium. Microbiol Rev 55: 561-585
35. Fujii N, Ishibashi Y, Satoh K, Fujino M and Harada K (1994) Simultaneous racemization and isomerization at specific aspartic acid residues in alpha B-crystallin from the aged human lens. Biochim Biophys Acta 1204: 157-163
36. Gafni A and Noy N (1984) Age-related effects in enzyme catalysis. Mol Cell Biochem 59: 113-129
37. Gineyts E, Cloos PAC, Borel O, Grimaud L, Delmas PD and Garnero P (2000) Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover. Biochem J 345: 481-485
38. Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C, Simon M, Senshu T, Masson-Bessiere C, Jolivet-Reynaud C, Jolivet M and Serre G (1999) The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol 162: 585-594
39. Goldbach-Mansky R, Lee J, McCoy A, Hoxworth J, Yarboro C, Smolen JS, Steiner G, Rosen A, Zhang C, Menard HA, Zhou ZJ, Palosuo T, Van Venrooij WJ, Wilder RL, Klippel JH, Schumacher HR Jr and El-Gabalawy HS (2000) Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res 2: 236-243
40. Harrison LC and Hafler DA (2000) Antigen specific therapy for autoimmune disease. Curr Opin Immunol 12: 704-717
41. Haynes BF, Sempowski GD, Wells AF and Hale LP (2000) The human thymus during aging. Immunol Res 22: 253-261
42. Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA and Cairns E (2003) The conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol 171: 538-541
43. Holmdahl R (2003) Dissection of the genetic complexity of arthritis using animal models. J Autoimmunol 21: 99-103
44. Ikeda K, Higashi T, Sano H, Jinnouchi Y, Yoshida M, Araki T, Ueda S and Horiuchi S. (1996) N(epsilon)-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction. Biochemistry 35: 8075-8083
45. Johnson BA and Aswad DW (1990) Fragmentation of isoaspartyl peptides and proteins by carboxypeptidase Y: release of isoaspartyl dipeptides as a result of internal and external cleavage. Biochemistry 29: 4373-4380
46. Kennelly PJ (2003) Archaeal protein kinases and protein phosphatases: insights from genomics and biochemistry. Biochem J 370: 373-389
47. Kim E, Lowenson JD, MacLaren DC, Clarke S and Young S (1997) Deficiency of a protein-repair enzyme results in the accumulation of altered proteins, retardation of growth, and fatal seizures in mice. Proc Natl Acad Sci USA 94: 6132-6137
48. Kim E, Lowenson JD, Clarke S and Young SG (1999) Phenotypic analysis of seizure-prone mice lacking L-isoaspartate (D-aspartate) O-methyltransferase. J Biol Chem 274: 20671-20678
49. Kim JH, Nam KH, Kwon OS, Kim IG, Bustin M, Choy HE and Park SC (2002) Histone cross-linking by transglutaminase. Biochem Biophys Res Commun 293: 1453-1457
50. Kovacic P and Jacintho JD (2003) Systemic lupus erythematosus and other autoimmune diseases from endogenous and exogenous agents: unifying theme of oxidative stress. Mini Rev Med Chem 3: 568-575
51. Kurien BT and Scofield RH (2003) Free radical mediated peroxidative damage in systemic lupus erythematosus. Life Sci 73: 1655-1666
52. Liu Y, Zhu B, Wang X, Luo L, Li P, Paty DW and Cynader MS (2003) Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis. J Neuroimmunol 139: 27-35
53. Lowenson JD and Clarke S (1992) Recognition of D-aspartyl residues in polypeptides by the erythrocyte L-isoaspartyl/D-aspartyl protein methyl-transferase. Implications for the repair hypothesis. J Biol Chem 267: 5985-5995
54. Lowenson JD, and Clarke S (1995) Recognition of isomerized and racemized aspartyl residues in peptides by the Protein L-isoaspartate (D-aspartate) O-methyltransferase. In: Aswad DW (ed) Deamidation and Isoaspartate Formation in Peptides and Proteins, pp. 47-64. CRC Press, Boca Raton, FL
55. Luo DF, Buzzetti R, Rotter JI, et al. (1996) Confirmation of three susceptibility genes to insulin dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8. Hum Mol Genet 5: 693-698
56. Mamula MJ (1998) Epitope spreading: the role of self peptides and autoantigen processing by B lymphocytes. Immunol Rev 164: 231-239
57. Mamula MJ, Gee RJ, Elliott JI, Sette A, Southwood S, Jones PJ and Blier PR (1999) Isoaspartyl post-translational modification triggers autoimmune responses to self-proteins. J Biol Chem 274: 22321-22327
58. Manoury B, Hewitt EW, Morrice N, Dando PM, Barrett AJ and Watts C (1998) An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. Nature 396: 695-699
59. Manoury B, Mazzeo D, Fugger L, Viner N, Ponsford M, Streeter H, Mazza G, Wraith DC and Watts C (2002) Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP. Nat Immunol 3:169-174
60. Manoury B, Mazzeo D, Li DN, Billson J, Loak K, Benaroch P and Watts C. (2003) Asparagine endopeptidase can initiate the removal of the MHC class II invariant chain chaperone. Immunity 18: 489-498
61. Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T and Serre G (2001) The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin. J Immunol 166: 4177-4184
62. McFadden PN and Clarke S (1987) Conversion of isoaspartyl peptides to normal peptides: implications for the cellular repair of damaged proteins. Proc Natl Acad Sci USA 84: 2595-2599
63. Menard HA, Lapointe E, Rochdi MD and Zhou ZJ (2000) Insights into rheumatoid arthritis derived from the Sa immune system Arthritis Res 2: 429-432
64. Miyata T, Ishiguro N, Yasuda Y, Ito T, Nangaku M, Iwata H and Kurokawa K (1998) Increased pentosidine, an advanced glycation end product, in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with inflammatory markers. Biochem Biophys Res Commun 244: 45-49
65. Mizoguchi M, Manabe M, Kawamura Y, Kondo Y, Ishidoh K, Kominami E, Watanabe K, Asaga H, Senshu T and Ogawa H (1998) Deimination of 70-kD nuclear protein during epidermal apoptotic events in vitro. J Histochem Cytochem 46: 1303-1309
66. Mohamed A, Shoker A, Bendjelloul F, Mare A, Alzrigh M, Benghuzzi H and Desin T (2003) Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; an oxidative stress inhibitor. Biomed Sci Instrum 39: 440-445
67. Molberg O, Mcadam SN, Korner R, Quarsten H, Kristiansen C, Madsen L, Fugger L, Scott H, Noren O, Roepstorff P, Lundin KE, Sjostrom H and Sollid LM (1998) Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 4: 713-717
68. Monneaux F, Lozano JM, Patarroyo ME, Briand JP and Muller S (2003) T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice. Eur J Immunol 33: 287-296
69. Moscarello MA, Wood DD, Ackerley C and Boulias C (1994) Myelin in multiple sclerosis is developmentally immature. J Clin Invest 94: 146-154
70. Myerscough A, John S, Barrett JH, Ollier WE and Worthington J (2000) Linkage of rheumatoid arthritis to insulin-dependent diabetes mellitus loci: evidence supporting a hypothesis for the existence of common autoimmune susceptibility loci. Arthritis Rheum 43: 2771-2775
71. Neugebauer KM, Merrill JT, Wener MH, et al. (2000) SR proteins are autoantigens in patients with systemic lupus erythromatosus: importance of phosphoepitopes. Arthritis Rheum 43: 1768-1778
72. Newkirk MM, Goldbach-Mansky R, Lee J, Hoxworth J, McCoy A, Yarboro C, Klippel J and El-Gabalawy HS (2003) Advanced glycation end-product (AGE)-damaged IgG and IgM autoantibodies to IgG-AGE in patients with early synovitis. Arthritis Res Ther 5: R82-R90
73. Olofson P, Holmberg J, Tordsson J, Lu S, Akerstrom B and Holmdahl R (2003) Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet 33: 25-32
74. Olofson P and Holmdahl R (2003) Positonal cloning of Ncf1-apiece in the puzzle of arthritis genetics. Scand J Immunol 58: 155-164
75. Penkowa M, Espejo C, Martinez-Caceres EM, Montalban X and Hidalgo J (2003) Increased demyelination and axonal damage in metallothionein I + II-deficient mice during experimental autoimmune encephalomyelitis. Cell Mol Life Sci 60: 185-197
76. Peterson DA, DiPaolo RJ, Kanagawa O and Unanue ER (1999) Cutting edge: negative selection of immature thymocytes by a few peptide-MHC complexes: differential sensitivity of immature and mature T cells. J Immunol 162: 3117-3120
77. Piacentini M and Colizzi V (1999) Tissue transglutaminase: apoptosis versus autoimmunity. Immunol Today 20: 130-134
78. Pritzker LB, Joshi S, Gowan JJ, Harauz G and Moscarello MA (2000) Deimination of myelin basic protein. 1. Effect of deimination of arginyl residues of myelin basic protein on its structure and susceptibility to digestion by cathepsin D. Biochemistry 39: 5374-5381
79. Quarsten H, Molberg O, Fugger L, McAdam SN and Sollid LM (1999) HLA binding and T cell recognition of a tissue transglutaminase-modified gliadin epitope. Eur J Immunol 29: 2506-2514
80. Radkiewicz JL, Zipse H, Clarke S and Houk KN (2001) Neighboring side chain effects on asparaginyl and aspartyl degradation: an ab initio study of the relationship between peptide conformation and backbone NH acidity. J Am Chem Soc 123: 3499-3506
81. Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H and van Venrooij W (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48: 2741-2749
82. Ritz-Timme S and Collins MJ (2002) Racemization of aspartic acid in human proteins. Ageing Res Rev 1: 43-59
83. Rodenburg RJ, Raats JM, Pruijn GJ and van Venrooij WJ. (2000) Cell death: a trigger of autoimmunity? Bioessays 22: 627-636
84. Rodriguez-Garcia J, Requena JR and Rodriguez-Segade S (1998) Increased concentrations of serum pentosidine in rheumatoid arthritis. Clin Chem 44: 250-255
85. Rudd PM, Elliott T, Cresswell P, Wilson IA and Dwek RA (2001) Glycosylation and the immune system. Science 291: 2370-2376
86. Sano H, Nagai R, Matsumoto K and Horiuchi S (1999) Receptors for proteins modified by advanced glycation end-products (AGE)-their functional role in atherosclerosis. Mech. Ageing Develop. 107: 333-346
87. Schellekens GA, de Jong BAW, van den Hoogen FHJ, van de Putte LBA and van Venrooij WJ (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis specific autoantibodies. J Clin Invest 101: 273-281
88. Sibilia J (2000) Autoantibodies, diagnostic and prognostic markers of rheumatoid polyarthritis. Presse Med 29: 1723-1730
89. Singh R, Barden A, Mori T and Beilin L (2001) Advanced glycation end-products: a review. Diabetologia 44: 129-146
90. Sollid LM (2000) Molecular basis of celiac disease. Annu Rev Immunol 18: 53-81
91. Sollid LM (2002) Coeliac disease: dissecting a complex inflammatory disorder. Nat Rev Immunol 2: 647-655
92. Sprent J and Kishimoto H (2002) The thymus and negative selection. Immunol Rev 185: 126-135
93. Stadtman ER and Berlet BS (1998) Reactive oxygen-mediated protein oxidation in aging and disease. Drug Metab Rev 30: 225-243
94. Stadtman ER (1992) Protein oxidation and aging. Science 257: 1220-1224
95. Stadtman ER (2001) Protein oxidation in aging and age-related diseases. Ann NY Acad Sci 928: 22-38
96. Stadtman ER, Oliver CN, Levine RL, Fucci L and Rivett AJ (1988) Implication of protein oxidation in protein turnover, aging, and oxygen toxicity. Basic Life Sci 49: 331-339
97. Steinman L (1996) Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell 85: 299-302
98. Stetler DA and Jacob ST (1984) Phosphorylation of RNA polymerase I augments its interaction with autoantibodies of systemic lupus erythematosus patients. J Biol Chem 259: 13629-13632
99. Suwannaroj S, Lagoo A, Keisler D and McMurray RW (2001) Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE). Lupus 10: 258-265
100. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, and Yamamoto K (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34: 395-402
101. Takahashi M, Suzuki M, Kushida K, Miyamoto S and Inoue T (1997) Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis. Br J Rheumatol 36: 637-642
102. Thornalley PJ (1998) Cell activation by glycated proteins. AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol (Noisy-le-grand) 44: 1013-1023
103. Trigwell SM, Radford PM, Page SR, Loweth AC, James RF, Morgan NG and Todd I (2001) Islet glutamic acid decarboxylase modified by reactive oxygen species is recognized by antibodies from patients with type 1 diabetes mellitus. Clin Exp Immunol 126: 242-249
104. Ulrich P and Cerami A (2001) Protein glycation, diabetes, and aging. Recent Prog Horm Res 56: 1-21
105. Urban L, Bessenyei B, Marka M and Semsei I (2002) On the role of aging in the etiology of autoimmunity. Gerontology 48: 179-184
106. Utz PJ, Hottelet M, Schur PH and Anderson P (1997) Proteins phosphorylated during stress induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med 185: 843-854
107. Utz PJ, Gensler TJ and Anderson P (2000) Death, autoantigen modifications, and tolerance. Arthritis Res 2: 101-114
108. van Stipdonk MJ, Willems AA, Amor S, Persoon-Deen C, Travers PJ, Boog CJ and van Noort JM (1998) T cells discriminate between differentially phosphorylated forms of alphaB-crystallin, a major central nervous system myelin antigen. Int Immunol 10: 943-950.
109. Virella G, Thorpe SR, Alderson NL, Stephan EM, Atchley D, Wagner F and Lopes-Virella MF (2003) Autoimmune response to advanced glycosylation end-products of human LDL. J Lipid Res 44: 487-493
110. Vlassara H (2001) The AGE-receptor in the pathogenesis of diabetic complications. Diabetes Metab Res Rev 17: 436-443
111. Vlassara H, Bucala R and Striker L (1994) Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 70: 138-151
112. Voorter CE, de Haard-Hoekman WA, Van den Oetelaar PJ, Bloemendal H, de Jong WW (1998) Spontaneous peptide bond cleavage in aging alpha-crystallin through a succinimide intermediate. J Biol Chem 263: 19020-19023
113. Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, Vasan S, Egan JJ, Ulrich P, Cerami A and Levy BI (1998) Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 95: 4630-4634
114. Wood DD, Bilbao JM, O'Connors P and Moscarello MA (1996) Acute multiple sclerosis (Marburg type) is associated with developmentally immature myelin basic protein. Ann Neurol 40: 18-24
115. Wuttge DM, Bruzelius M and Stemme S (1999) T-cell recognition of lipid peroxidation products breaks tolerance to self proteins. Immunology 98: 273-279
116. Yagi J and Janeway CA Jr (1990) Ligand thresholds at different stages of T cell development. Int Immunol 2: 83-89
117. Young AL, Carter WG, Doyle HA, Mamula MJ and Aswad DW (2001) Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartate O-methyltransferase, a putative protein repair enzyme. J Biol Chem 276: 37161-37165
118. Zampieri S, Degen W, Ghiradello A, Doria A and van Venrooij WJ (2001) Dephosphorylation of autoantigenic ribosomal P proteins during Fas-L induced apoptosis: a possible trigger for the development of the autoimmune response in patients with systemic lupus erythematosus. Ann Rheum Dis 60: 72-76
119. Zamvil SS, Mitchell DJ, Moore AC, Kitamura K, Steinman L and Rothbard JB (1986) T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324: 258-260