A common epitope on human tumor necrosis factor alpha and the autoantigen ‘S-antigen/arrestin’ induces TNF-α production

Co-purification of arrestin like proteins with alpha-enolase from bovine myocardial tissues and the possible role in heart diseases as an autoantigen

“…Several mouse and rat monoclonal antibodies (mAbs) against retinal arrestin were produced [16] and characterized by epitope mapping employing combinations of two methods, namely, overlapping of synthetic peptides and petscan analysis as described previously [17]. Antibodies S8D8 (mouse IgG2a aa 40e50), S9E2 (mouse IgG2a, aa 361e368) and rat mAb M1E5 (rat IgG1, aa 279e306) were produced as previously reported [16,18].…”

Induction or suppression of a B cell-specific response to self antigenin vivo is dependent upon dendritic cell activation via the TNF-α receptor at the time of antigen uptake

“…Overall pixel intensity was also reduced significantly in the S-antigen-treated explants compared with those treated with TNF- § (p=0.001). This may represent an additional effect of S-antigen through autocrine stimulation of TNF- § secretion by tissue macrophages also present in large numbers in the choroid [16,23]. Morphological appearance and pixel intensity measurements were restored to control levels by pretreatment of explants with p55TNFR-Ig fusion protein.…”

“…Thus, induction of immunity or anergy may depend not on the antigen-presenting cell (APC), or indeed on whether the antigen is "foreign" or "self", but on whether antigen challenge is accompanied by other signals such as bacterial endotoxins or inflammatory cytokines. The purpose of this study was to test this hypothesis by examining the ability of DC from a single precursor population to induce immunity to "self" antigens in vivo using two retinal autoantigens, one of which contains microbial and TNF- § sequence homologies [15][16][17]. The retina of the eye is isolated from normal immune surveillance by the blood-retina barrier and is the source of a number of autoantigens implicated in the pathogenesis of endogenous posterior uveoretinitis, a retinal inflammation leading to considerable loss of vision [18].…”

“…Both are soluble, and exhibit sequence homology between species. Santigen also has five highly conserved motifs defined for all known arrestin sequences [19], including motif I [amino acids (aa) which contains a common epitope with human TNF- § [16], and motif IV (aa 286-304) which spans the highly uveitogenic peptide N [20]. In addition, the uveitogenic peptide M (aa 303-320), has homology with several microbial proteins [17].…”

“…In addition, the uveitogenic peptide M (aa 303-320), has homology with several microbial proteins [17]. S-antigen and S-antigen peptide (peptide 40-50) containing the minimum common epitope of TNF- § (GVXLXD), have been shown to induce autocrine TNF- § production in monocytes [16]. Sequestration of this potentially "dangerous" antigen behind the blood-retina barrier, an environment devoid of conventional DC, has been shown to be an important contribution to retinal immune privilege [21].…”