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Structure-function studies of S-antigen: use of proteases to reveal a dominant uveitogenic site

Structure-function studies of S-antigen: use of proteases to reveal a dominant uveitogenic site
Structure-function studies of S-antigen: use of proteases to reveal a dominant uveitogenic site
Retinal S-antigen induced experimental autoimmune uveitis (EAU) is a severe, predominantly T-cell mediated inflammatory disease of the uveal tract and retina of the eye. Pretreatment of LEW rats with the monoclonal antibody, MAbS2.4.C5, which defines an epitope in S-antigen, has been shown to effectively inhibit the subsequent induction of EAU with S-antigen. Using synthetic peptides and cyanogen bromide fragments of S-antigen we found the binding site of MAbS2.4.C5 to be located at the carboxy terminus of the molecule corresponding to amino acid positions 375 to 380. Limited Staphylococcus aureus V8 protease digestion yielded several polypeptide fragments including one large 43 kD fragment which retained antibody binding to a variety of both polyclonal and monoclonal antibodies which identify epitopes that span the length of the S-antigen. This treatment, however, completely destroys the MAbS2.4.C5 binding site and dramatically reduces uveitopathogenicity. Limited trypsin and papain digestion, on the other hand, had little effect on pathogenicity or on MAbS2.4.C5 binding to S-antigen or its peptide fragments. These results indicate that the carboxy-terminus of S-antigen plays a predominant role in the pathogenesis of EAU.
0891-6934
153-163
Dua, H
7b97f9fe-cfcc-4b7b-a428-d5bff180d3a5
Hossain, P
563de5fc-84ad-4539-9228-bde0237eaf51
Brown, P A
99ae5ab1-0e3e-4db5-9103-e813392f4621
McKinnon, A
4e83d886-f4a2-46b3-adac-f772549f0c27
Forrester, J
790c966a-5b4f-4e3a-ad20-694a69b76c8c
Gregerson, D
613570c6-b76d-40b7-bf37-7be741e2fdf4
Donoso, L
1bb07a79-36da-4ed9-880a-2a44f1facc41
Dua, H
7b97f9fe-cfcc-4b7b-a428-d5bff180d3a5
Hossain, P
563de5fc-84ad-4539-9228-bde0237eaf51
Brown, P A
99ae5ab1-0e3e-4db5-9103-e813392f4621
McKinnon, A
4e83d886-f4a2-46b3-adac-f772549f0c27
Forrester, J
790c966a-5b4f-4e3a-ad20-694a69b76c8c
Gregerson, D
613570c6-b76d-40b7-bf37-7be741e2fdf4
Donoso, L
1bb07a79-36da-4ed9-880a-2a44f1facc41

Dua, H, Hossain, P, Brown, P A, McKinnon, A, Forrester, J, Gregerson, D and Donoso, L (1991) Structure-function studies of S-antigen: use of proteases to reveal a dominant uveitogenic site Autoimmunity, 10, (2), pp. 153-163. (PMID:1723632).

Record type: Article

Abstract

Retinal S-antigen induced experimental autoimmune uveitis (EAU) is a severe, predominantly T-cell mediated inflammatory disease of the uveal tract and retina of the eye. Pretreatment of LEW rats with the monoclonal antibody, MAbS2.4.C5, which defines an epitope in S-antigen, has been shown to effectively inhibit the subsequent induction of EAU with S-antigen. Using synthetic peptides and cyanogen bromide fragments of S-antigen we found the binding site of MAbS2.4.C5 to be located at the carboxy terminus of the molecule corresponding to amino acid positions 375 to 380. Limited Staphylococcus aureus V8 protease digestion yielded several polypeptide fragments including one large 43 kD fragment which retained antibody binding to a variety of both polyclonal and monoclonal antibodies which identify epitopes that span the length of the S-antigen. This treatment, however, completely destroys the MAbS2.4.C5 binding site and dramatically reduces uveitopathogenicity. Limited trypsin and papain digestion, on the other hand, had little effect on pathogenicity or on MAbS2.4.C5 binding to S-antigen or its peptide fragments. These results indicate that the carboxy-terminus of S-antigen plays a predominant role in the pathogenesis of EAU.

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Published date: 1991

Identifiers

Local EPrints ID: 193075
URI: http://eprints.soton.ac.uk/id/eprint/193075
ISSN: 0891-6934
PURE UUID: b1771bcc-fca2-405f-8976-568175a2ddc5
ORCID for P Hossain: ORCID iD orcid.org/0000-0002-3131-2395

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Date deposited: 12 Jul 2011 08:45
Last modified: 18 Jul 2017 11:30

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Contributors

Author: H Dua
Author: P Hossain ORCID iD
Author: P A Brown
Author: A McKinnon
Author: J Forrester
Author: D Gregerson
Author: L Donoso

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