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Titolo:
Search for the autoantibody immunodominant region on thyroid peroxidase: Epitopic footprinting with a human monoclonal autoantibody locates a facet on the native antigen containing a highly conformational epitope
Autore:
Guo, J; Yan, XM; McLachlan, SM; Rapoport, B;
Indirizzi:
Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90048 USA Univ Calif Los Angeles Los Angeles CA USA 90048 Los Angeles, CA 90048 USA Cedars Sinai Res Inst, Autoimmune Dis Unit, Los Angeles, CA 90048 USA Cedars Sinai Res Inst Los Angeles CA USA 90048 Los Angeles, CA 90048 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 2, volume: 166, anno: 2001,
pagine: 1327 - 1333
SICI:
0022-1767(20010115)166:2<1327:SFTAIR>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
B-CELL EPITOPE; IMMUNOGLOBULIN GENE USAGE; HASHIMOTOS-THYROIDITIS; CRYSTAL-STRUCTURE; RECOMBINANT; DISEASE; FAB; THYROPEROXIDASE; RECOGNITION; FRAGMENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Rapoport, B Cedars Sinai Med Ctr, Autoimmune Dis Unit, 8700 Beverly Blvd,suite B-131, Los Angeles, CA 90048 USA Cedars Sinai Med Ctr 8700 Beverly Blvd,suite B-131 Los Angeles CA USA 90048
Citazione:
J. Guo et al., "Search for the autoantibody immunodominant region on thyroid peroxidase: Epitopic footprinting with a human monoclonal autoantibody locates a facet on the native antigen containing a highly conformational epitope", J IMMUNOL, 166(2), 2001, pp. 1327-1333

Abstract

Autoantibodies to thyroid peroxidase (TPO) are the hallmark of the humoralautoimmune response in human autoimmune thyroiditis (Hashimoto's thyroiditis). The majority of TPO autoantibodies in individual patients' sera interact with a restricted immunodominant region on TPO. Although this region canbe mapped, previous studies have failed to localize its position on the TPO molecule. We, therefore, used a footprinting approach that can localize ahighly conformational, discontinuous epitope on a very large molecule. Extensive biotinylation (similar to 15 biotins/molecule protein:) of lysine residues on the surface of purified, native TPO resulted in loss of multiple tryptic cleavage sites, as determined by analysis of tryptic polypeptide fragments on reverse-phase HPLC. TPO was then complexed with a monoclonal human autoantibody Fab (TR1.9) before biotinylation. After dissociation from TR1.9, TPO was recovered by gel filtration. A trypsin site, previously observed to be lost after TPO biotinylation, was restored when biotinylation wasperformed on the TPO-TR1.9 complex. The epitope-protected lysine (K) was present in a 30-aa TPO fragment that, by N-terminal sequencing, was found tobe K713. Altered recognition by TR1.9 of a TBO-myeloperoxidase chimeric molecule involving this region supported the epitope protection data. In conclusion, we provide the first identification of an amino acid residue (K713)comprising part of an epitope within the TPO Immunodominant region. This focal residue localizes the facet on the large, highly complex TPO molecule that contains the immunodominant region and provides the basis for rationalguided mutagenesis studies to more fully characterize this region.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 07:55:15