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Structure-function studies of S-antigen: use of proteases to reveal a dominant uveitogenic site.
- Source :
-
Autoimmunity [Autoimmunity] 1991; Vol. 10 (2), pp. 153-63. - Publication Year :
- 1991
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal therapeutic use
Antigens chemistry
Antigens drug effects
Arrestin
Autoantigens chemistry
Autoimmune Diseases prevention & control
Binding Sites, Antibody
Endopeptidases pharmacology
Epitopes immunology
Eye Proteins chemistry
Eye Proteins drug effects
Female
Molecular Sequence Data
Peptide Fragments chemical synthesis
Peptide Fragments immunology
Rats
Rats, Inbred Lew immunology
Structure-Activity Relationship
Uveitis prevention & control
Antibodies, Monoclonal immunology
Antigens immunology
Autoantigens immunology
Autoimmune Diseases immunology
Eye Proteins immunology
Uveitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0891-6934
- Volume :
- 10
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 1723632
- Full Text :
- https://doi.org/10.3109/08916939109004819