Repertoire Analysis and New Pathogenic Epitopes of IRBP in C57BL/6 (H-2^b) and B10.RIII (H-2^r) Mice

Abstract

Several new pathogenic peptides of IRBP were identified in C57BL/6 and B10.RIII mice. Differences in epitope recognition between WT and IRBP KO mice were observed in C57BL/6 mice, but not in B10.RIII mice, suggesting more extensive culling of the repertoire in C57BL/6 mice by endogenously expressed IRBP.

A novel pathogenic RBP‐3 peptide reveals epitope spreading in persistent experimental autoimmune uveoretinitis

“…Together these data pointed to the presence of a pathogenic epitope or epitopes within subunit 3. As the severity of disease induced by this subunit was greater than that previously reported for the non-immunodominant peptide 651-670, 12 this raised the possibility that additional epitopes might be present.…”

“…Human RBP-3 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Peptide (GPTHLFQPSLVLDMAKV LLD) and chicken ovalbumin (OVA) (ISQAVHAAHAEIN EAGR) were synthesized by Sigma-Aldrich (Poole, UK).…”

“…We then examined the individual T-cell responses from mice immunized with RBP-3 629-643 peptide and recalled with the immunizing antigen and the non-immunizing peptide. Both the immunizing peptide (629-643) and the epitope to which reactivity had spread (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) induced proliferation that positively correlated [r = 0Á35 (P < 0Á05), r = 0Á49 (P < 0Á01)] with the level of clinical disease (Fig. 5f,g).…”

Experimental models of autoimmune inflammatory ocular diseases

“…This EAU model differs in immunological, clinical, and pathological characteristics from the traditional IRBP-CFA model, in which the disease is shorter and less severe. The fundus lesions are punctates and there are more neutrophils than monocytes (48) . This autoimmune uveitis model demonstrates that the same antigen may induce different forms of uveitis, depending on how they are presented to the immune system, and may help to explain the heterogeneity of human uveitis (48) .…”

“…Approximately 84% of the bovine and human IRBP present identical sequence of amino acids (44,45) . Many studies using EAU models induced by IRBP have aimed the identification of the exact immunogenic epitopes (46)(47)(48) and interactions with the MHC molecules. Specific IRBP epitopes ha ve already been recognized as uveitogenic in susceptible mice strains: Peptide 1-20 for C57BL/6, 161-180 for B10.RIII, and 201-216 for B10.A (49) , and recent studies revealed several additional uveitogenic epitopes of human IRBP molecule that elicit EAU in mice (48) .…”