Cytokine induction by immunomodulatory epitopes in S-antigen and tumor necrosis factor alpha.
Common epitopes on S-antigen (arrestin), a potent autoantigen inducing experimental autoimmune uveoretinitis (EAU), and on human tumor necrosis factor alpha (hTNF alpha) are revealed with monoclonal antibodies (mAb) to S-antigen, which inhibit EAU induction. The minimal common sequence for mAb recognition is GVxLxD in the S-antigen/hTNF alpha amino acid (aa) sequences. Peptides containing this sequence motif exhibit monocyte activating capacity analogous to the autocrine stimulatory capacity of hTNF alpha itself. In S-antigen this activity is located at epitope S2 (aa residues 40 to 50), corresponding to the peptide PVDGVVLVDPE (peptide S2). In hTNF alpha the monocyte activating capacity correlates to aa residue 31 to 53, corresponding to the peptide RRANALLANGVELRDNQLVVPSE (peptide RRAN). Peptide S2 but not peptide RRAN is competing for mAbs S6H8 and S2D2 binding to S-antigen. Anti-idiotypic antibodies to S2D2 compete with peptide S2 but not peptide RRAN for binding to mAbs S2D2 and S6H8. In human retinal S-antigen epitope S2 is localized at the aa residues 44-54 and is cleaved in the human peptide 4 (aa 31-50). Competition experiments with peptide 4 (aa 31-50) and peptide 5 (aa 41-60) indicate that the C-terminal aa residues VDPD in the epitope S2 play an important role for internal image recognition of the anti-idiotypic antibodies. Peptide S2 and peptide RRAN define common functional structures in the autoantigen and hTNF alpha molecules. The data suggest regulatory functions of the peptides in cytokine expression, network regulation and in autoimmunity.
Stiemer
R H
RH
Laboratoire d'Immunopathologie de l'Oiel, INSERM U 86, Paris, France.
Westenfelder
U
U
de Kozak
Y
Y
Gausepohl
H
H
Mirshahi
M
M
Frank
R W
RW
Faure
J P
JP
Männel
D N
DN
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000276:immunology*; D019393:Arrestin; D001324:Autoantigens / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D016207:Cytokines; D000939:Epitopes; D005136:Eye Proteins; D014409:Tumor Necrosis Factor-alpha