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Titolo:
Dominant autoimmune epitopes recognized by pemphigus antibodies map to theN-terminal adhesive region of desmogleins
Autore:
Sekiguchi, M; Futei, Y; Fujii, Y; Iwasaki, T; Nishikawa, T; Amagai, M;
Indirizzi:
Keio Univ, Sch Med, Dept Dermatol, Shinjuku Ku, Tokyo 1608582, Japan Keio Univ Tokyo Japan 1608582 ermatol, Shinjuku Ku, Tokyo 1608582, Japan Tokyo Univ Agr & Technol, Fac Vet Med, Dept Internal Med, Tokyo 156, JapanTokyo Univ Agr & Technol Tokyo Japan 156 Internal Med, Tokyo 156, Japan
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 9, volume: 167, anno: 2001,
pagine: 5439 - 5448
SICI:
0022-1767(20011101)167:9<5439:DAERBP>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLISTER-CAUSING ANTIBODIES; CELL-CELL ADHESION; VULGARIS ANTIGEN; PATHOGENIC AUTOANTIBODIES; DESMOSOMAL CADHERINS; EPITHELIAL CADHERIN; STRUCTURAL BASIS; NEONATAL MICE; MOLECULES; DOMAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Amagai, M Keio Univ, Sch Med, Dept Dermatol, Shinjuku Ku, 35 Shinanomachi,Tokyo 1608582, Japan Keio Univ 35 Shinanomachi Tokyo Japan 1608582 yo 1608582, Japan
Citazione:
M. Sekiguchi et al., "Dominant autoimmune epitopes recognized by pemphigus antibodies map to theN-terminal adhesive region of desmogleins", J IMMUNOL, 167(9), 2001, pp. 5439-5448

Abstract

Desmoglein (Dsg) is a cadherin-type adhesion molecule found in desmosomes. Dsg1 and Dsg3 are the target Ags in the autoimmune blistering diseases pemphigus foliaceus (PF) and pemphigus vulgaris (PV), respectively. To map conformational epitopes of Dsg1 and Dsg3 in PF and PV, we generated Dsg1- and Dsg3-domain-swapped molecules and point-mutated Dsg3 molecules with Dsg1-specific residues by baculovirus expression. The swapped domains were portions of the N-terminal extracellular domains of Dsg1 (1-496) and Dsg3 (1-566),which have similar structures but distinct epitopes. The binding of autoantibodies to the mutant molecules was assessed by competition ELISAs. Domain-swapped molecules containing the N-terminal 161 residues of Dsg1 and Dsg3 yielded > 50% competition in 30/43 (69.8%) PF sera and 31/40 (77.5%) PV sera, respectively. Furthermore, removal of Abs against the 161 N-terminal residues of Dsg1 by immunoadsorption eliminated the ability of PIT sera to induce cutaneous blisters in neonatal mice. Within these N-terminal regions, most of the epitopes were mapped to residues 26-87 of Dsg1 and 25-88 of Dsg3. Furthermore, a point-mutated Dsg3 molecule containing Dsg1-specific aminoacid substitutions (His(25), Cys(28), Ala(29)) reacted with anti-Dsg1 IgG,thus defining one of the epitopes of Dsg1. Using the predicted three-dimensional structure of classic cadherins as a model, these findings suggest that the dominant autoimmune epitopes in both PF and PV are found in the N-terminal adhesive surfaces of Dsgs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 10:31:22