COOH-terminal clustering of autoantibody and T-cell determinants on the structure of GAD65 provide insights into the molecular basis of autoreactivity

Diabetes

Volumn 57, Issue 5, 2008, Pages 1293-1301

  Fenalti, Gustavo ^a   Hampe, Christiane S ^b   Arafat, Yasir ^a   Law, Ruby H P ^a   Banga, J Paul ^c   Mackay, Ian R ^a   Whisstock, James C ^a   Buckle, Ashley M ^a   Rowley, Merrill J ^a,d  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF WASHINGTON   (United States)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; EPITOPE; GLUTAMATE DECARBOXYLASE 65; GLUTAMATE DECARBOXYLASE 67; HLA DR ANTIGEN; IMMUNOGLOBULIN F(AB) FRAGMENT; MONOCLONAL ANTIBODY; PYRIDOXAL 5 PHOSPHATE; GLUTAMATE DECARBOXYLASE; GLUTAMATE DECARBOXYLASE 1; GLUTAMATE DECARBOXYLASE 2; PEPTIDE FRAGMENT;

AMINO TERMINAL SEQUENCE; ANTIBODY STRUCTURE; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CRYSTAL STRUCTURE; EPITOPE MAPPING; HUMAN; HUMAN CELL; INSULIN DEPENDENT DIABETES MELLITUS; MUTAGENESIS; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; RADIOIMMUNOPRECIPITATION; T LYMPHOCYTE; ANTIBODY COMBINING SITE; AUTOIMMUNE DISEASE; CHEMICAL STRUCTURE; CHEMISTRY; DIMERIZATION; ENZYMOLOGY; GENETICS; IMMUNOLOGY; KINETICS; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

ANTIBODIES, MONOCLONAL; AUTOANTIBODIES; AUTOIMMUNE DISEASES; B-LYMPHOCYTES; BINDING SITES, ANTIBODY; CRYSTALLOGRAPHY, X-RAY; DIABETES MELLITUS, TYPE 1; DIMERIZATION; EPITOPES; GLUTAMATE DECARBOXYLASE; HUMANS; KINETICS; MODELS, MOLECULAR; MUTAGENESIS; PEPTIDE FRAGMENTS; PROTEIN CONFORMATION; T-LYMPHOCYTES;

EID: 48449102723     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db07-1461     Document Type: Article

References (41)

1. Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P: Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347:151-156, 1990
2. Lernmark A: Glutamic acid decarboxylase: gene to antigen to disease. J Intern Med 240:259-277, 1996
3. Schlosser M, Banga JP, Madec AM, Binder KA, Strebelow M, Rjasanowski I, Wassmuth R, Gilliam LK, Luo D, Hampe CS: Dynamic changes of GAD65 autoantibody epitope specificities in individuals at risk of developing type 1 diabetes. Diabetologia 48:922-930, 2005
4. Schwartz HL, Chandonia JM, Kash SF, Kanaani J, Tunnell E, Domingo A, Cohen FE, Banga JP, Madec AM, Richter W, Baekkeskov S: High-resolution autoreactive epitope mapping and structural modeling of the 65 kDa form of human glutamic acid decarboxylase. J Mol Biol 287:983-999, 1999
5. Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC: GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. Nat Struct Mol Biol 14:280-286, 2007
6. Richter W, Endl J, Eiermann TH, Brandt M, Kientsch-Engel R, Thivolet C, Jungfer H, Scherbaum WA: Human monoclonal islet cell antibodies from a patient with insulin-dependent diabetes mellitus reveal glutamate decar-boxylase as the target antigen. Proc Natl Acad Sci USA. 89:8467-8471, 1992
7. Madec AM, Rousset F, Ho S, Robert F, Thivolet C, Orgiazzi J, Lebecque S: Four IgG anti-islet human monoclonal antibodies isolated from a type 1 diabetes patient recognize distinct epitopes of glutamic acid decarboxylase 65 and are somatically mutated. J Immunol 156:3541-3549, 1996
8. Tremble J, Morgenthaler NG, Vlug A, Powers AC, Christie MR, Scherbaum WA, Banga JP: Human B cells secreting immunoglobulin G to glutamic acid decarboxylase-65 from a nondiabetic patient with multiple autoantibodies and Graves' disease: a comparison with those present in type 1 diabetes. J Clin Endocrinol Metab 82:2664-2670, 1997
9. Powers AC, Bavik K, Tremble J, Daw K, Scherbaum WA, Banga JP: Comparative analysis of epitope recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different autoimmune disorders. Clin Exp Immunol 118:349-356, 1999
10. O'Connor KH, Banga JP, Darmanin C, El-Kabbani O, Mackay IR, Rowley MJ: Characterisation of an autoreactive conformational epitope on GAD65 recognised by the human monoclonal antibody b78 using a combination of phage display, in vitro mutagenesis and molecular modelling. J Autoimmun 26:172-181, 2006
11. Fenalti G, Hampe CS, O'Connor K, Banga JP, Mackay IR, Rowley MJ, El-Kabbani O: Molecular characterization of a disease associated confor-mational epitope on GAD65 recognised by a human monoclonal antibody b96.11. Mol Immunol 44:1178-1189, 2007
12. Teoh KL, Fida S, Rowley MJ, Mackay IR: Autoantigenic reactivity of diabetes sera with a hybrid glutamic acid decarboxylase GAD67-65 molecule GAD67(1-101)/GAD65(96-585). Autoimmunity 28:259-266, 1998
13. Powell M, Prentice L, Asawa T, Kato R, Sawicka J, Tanaka H, Petersen V, Munkley A, Morgan S, Rees Smith B, Furmaniak J: Glutamic acid decar-boxylase autoantibody assay using 125I-labelled recombinant GAD65 produced in yeast. Clin Chim Acta 256:175-188, 1996
14. Primo ME, Anton EA, Villanueva AL, Poskus E, Ermacora MR: Engineered variants of human glutamic acid decarboxylase (GAD) and autoantibody epitope recognition. Clin Immunol 108:38-45, 2003
15. DeLano WL: The PyMOL User's Manual (2002) [online], 2002. San Carlos, CA, DeLano Scientific. Available from http://www.pymol.org
16. Konagurthu AS, Whisstock JC, Stuckey PJ, Lesk AM: MUSTANG: a multiple structural alignment algorithm. Proteins 64:559-574, 2006
17. Padoa CJ, Banga JP, Madec AM, Ziegler M, Schlosser M, Ortqvist E, Kockum I, Palmer J, Rolandsson O, Binder KA, Foote J, Luo D, Hampe CS: Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetes-specific GAD65Abs. Diabetes 52:2689-2695, 2003
18. Lonnrot M, Hyoty H, Knip M, Roivainen M, Kulmala P, Leinikki P, Akerblom HK: Antibody cross-reactivity induced by the homologous regions in glutamic acid decarboxylase (GAD65) and 2C protein of coxsackievirus B4: Childhood Diabetes in Finland Study Group. Clin Exp Immunol 104:398-405, 1996
19. Patel SD, Cope AP, Congia M, Chen TT, Kim E, Fugger L, Wherrett D, Sonderstrup-McDevitt G: Identification of immunodominant T cell epitopes of human glutamic acid decarboxylase 65 by using HLA-DR(alpha1*0101,beta1 *0401) transgenic mice. Proc Natl Acad Sci USA 94:8082-8087, 1997
20. Nepom GT, Lippolis JD, White FM, Masewicz S, Marto JA, Herman A, Luckey CJ, Falk B, Shabanowitz J, Hunt DF, Engelhard VH, Nepom BS: Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65). Proc Natl Acad Sci USA 98:1763-1768, 2001
21. Wicker LS, Chen SL, Nepom GT, Elliott JF, Freed DC, Bansal A, Zheng S, Herman A, Lernmark A, Zaller DM, Peterson LB, Rothbard JB, Cummings R, Whiteley PJ: Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes-associated human MHC class II allele, DRB1*0401. J Clin Invest 98:2597-2603, 1996
22. Raju R, Foote J, Banga JP, Hall TR, Padoa CJ, Dalakas MC, Ortqvist E, Hampe CS: Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients. J Immunol 175:7755-7762, 2005
23. Hampe CS, Nalini R, Maldonado MR, Hall TR, Garza G, Iyer D, Balasubra-manyam A: Association of amino-terminal-specific antiglutamate decar-boxylase (GAD65) autoantibodies with beta-cell functional reserve and a milder clinical phenotype in patients with GAD65 antibodies and ketosis-prone diabetes mellitus. J Clin Endocrinol Metab 92:462-467, 2007
24. Hampe CS, Kockum I, Landin-Olsson M, Torn C, Ortqvist E, Persson B, Rolandsson O, Palmer J, Lernmark A: GAD65 antibody epitope patterns of type 1.5 diabetic patients are consistent with slow-onset autoimmune diabetes. Diabetes Care 25:1481-1482, 2002
25. Kobayashi T, Tanaka S, Okubo M, Nakanishi K, Murase T, Lernmark A: Unique epitopes of glutamic acid decarboxylase autoantibodies in slowly progressive type 1 diabetes. J Clin Endocrinol Metab 88:4768-4775, 2003
26. Richter W, Seissler J, Northemann W, Wolfahrt S, Meinck HM, Scherbaum WA: Cytoplasmic islet cell antibodies recognize distinct islet antigens in IDDM but not in stiff man syndrome. Diabetes 42:1642-1648, 1993
27. Panina-Bordignon P, Lang R, van Endert PM, Benazzi E, Felix AM, Pastore RM, Spinas GA, Sinigaglia F: Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med 181:1923-1927, 1995
28. Mackay IR, Rowley MJ: Autoimmune epitopes: autoepitopes. Autoimmun Rev 3:487-492, 2004
29. Jaume JC, Parry SL, Madec AM, Sonderstrup G, Baekkeskov S: Suppres-sive effect of glutamic acid decarboxylase 65-specific autoimmune B lymphocytes on processing of T cell determinants located within the antibody epitope. J Immunol 169:665-672, 2002
30. Banga JP, Moore JK, Duhindan N, Madec AM, van Endert PM, Orgiazzi J, Endl J: Modulation of antigen presentation by autoreactive B cell clones specific for GAD65 from a type I diabetic patient. Clin Exp Immunol 135:74-84, 2004
31. Reijonen H, Daniels TL, Lernmark A, Nepom GT: GAD65-specific autoan-tibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes 49:1621-1626, 2000
32. Wong FS, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J, Hannum LG, Janeway CA Jr, Shlomchik MJ: Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 53:2581-2587, 2004
33. Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ: B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol 177:4481-4487, 2006
34. Quaratino S, Ruf J, Osman M, Guo J, McLachlan S, Rapoport B, Londei M: Human autoantibodies modulate the T cell epitope repertoire but fail to unmask a pathogenic cryptic epitope. J Immunol 174:557-563, 2005
35. Plotz PH: The autoantibody repertoire: searching for order. Nat Rev Immunol 3:73-78, 2003
36. Paus D, Winter G: Mapping epitopes and antigenicity by site-directed masking. Proc Natl Acad SciUSA103:9172-9177, 2006
37. Nair DT, Singh K, Siddiqui Z, Nayak BP, Rao KV, Salunke DM: Epitope recognition by diverse antibodies suggests conformational convergence in an antibody response. J Immunol 168:2371-2382, 2002
38. Tainer JA, Getzoff ED, Paterson Y, Olson AJ, Lerner RA: The atomic mobility component of protein antigenicity. Annu Rev Immunol 3:501-535, 1985
39. Thornton JM, Edwards MS, Taylor WR, Barlow DJ: Location of 'continuous' antigenic determinants in the protruding regions of proteins. EMBO J 5:409-413, 1986
40. Estienne V, Duthoit C, Blanchin S, Montserret R, Durand-Gorde JM, Chartier M, Baty D, Carayon P, Ruf J: Analysis of a conformational B cell epitope of human thyroid peroxidase: identification of a tyrosine residue at a strategic location for immunodominance. Int Immunol 14:359-366, 2002
41. Kim SJ, Jeong DG, Jeong SK, Yoon TS, Ryu SE: Crystal structure of the major diabetes autoantigen insulinoma-associated protein 2 reveals distinctive immune epitopes. Diabetes 56:41-48, 2007