Idiotype-anti-idiotype circuit in non-autoimmune mice after immunization with the epitope and complementary epitope 289-308aa of La/SSB: implications for the maintenance and perpetuation of the anti-La/SSB response.
BACKGROUND
Antibodies to La/SSB are usually found in sera of patients with Sjogren's Syndrome (SS) and Systemic Lupus Erythematosus (SLE). Recent work from our laboratory (Mol Med 2002;8:293-305) revealed that an active idiotypic network involving antibodies to epitopes of La/SSB and their anti-idiotypes exist in human sera. The anti-idiotypic antibodies were detected using complementary peptides to B-cell epitopes of the autoantigen. The principle of the complementary peptides is based on the 'molecular recognition' theory. According to this theory, translation of two complementary RNA strands (coding and non-coding strand) into protein, generate a pair of peptides, which bind each other with specificity and high affinity.


OBJECTIVE
To investigate antibody production and T-cell responses in non-autoimmune-susceptible animal strains which were immunized with the epitope 289-308aa of La/SSB as well as its complementary epitope.


METHODS
Balb/c mice were immunized with a peptide corresponding to epitope 289-308aa (pep) or its complementary (cpep) peptide (5 animals/group). The sera were tested for the presence of antibodies to pep and cpep as well as for epitope spreading to recombinant human La/SSB and a major B-cell epitope of La/SSB spanning the region 349-364aa. Another group of animals was sacrificed on day 10 and T-cell responses against pep and cpep were evaluated in cells from lymph nodes and spleen.


RESULTS
Immunizations with either pep or cpep led to the appearance of antibodies against the immunogen peptide by day 31 which subsequently was followed by antibody production to its complementary peptide by day 55. In two out of five animals immunized with the epitope 289-308aa, a spreading of the immune response to epitope 349-364aa was observed. In the remaining three animals, negative for antibodies to pep349-364, a specific treatment of sera, using cpep349-364 revealed that anti-idiotypic antibodies masked antibodies to pep349-364. In all immunization experiments high T-cell proliferative responses to both pep and cpep peptides were detected.


CONCLUSIONS
Complementary peptides to epitopes of La/SSB can be utilized as probes to study the development of an idiotypic-anti-idiotypic network towards the major autoantigen. The ability of pep and cpep peptides to induce both B-cell and T-cell responses may provide useful insights into understanding further the initiation and maintenance of autoimmune response and create new tools for therapeutic intervention.
Routsias
John G
JG
Department of Pathophysiology, School of Medicine, University of Athens, Greece. jroutsias@med.uoa.gr
Dotsika
Eleni
E
Touloupi
Eugenia
E
Papamattheou
Maria
M
Sakarellos
Constantinos
C
Sakarellos-Daitsiotis
Maria
M
Moutsopoulos
Haralampos M
HM
Tzioufas
Athanasios G
AG
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001324:Autoantigens; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000276:immunology* / Q000494:pharmacology; D014612:Vaccines / Q000494:pharmacology; D000097585:SS-B Antigen
D000906:Antibodies; D001324:Autoantigens; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D010455:Peptides; D012261:Ribonucleoproteins; D014612:Vaccines; D000097585:SS-B Antigen