A complementary peptide vaccine that induces T cell anergy and prevents experimental allergic neuritis in Lewis rats.
We have developed and described a new method of altering T cell-mediated autoimmune diseases by immunization with the complementary peptide against T cell epitopes. The complementary peptide (denoted NAE 07-06) to the bovine P2 protein, residues 60-70 (denoted EAN 60-70), was tested in the Lewis rat model of experimental allergic neuritis (EAN). Immunization with NAE 07-06 induced polyclonal and monoclonal Abs that inhibited the proliferation of the P2-specific T cell line, stimulated with EAN 60-70, and recognized Vbeta, but not Valpha, of TCRs. Proliferation of T cells treated with anti-NAE 07-06 Abs could be partially restored by treatment with rIL-2, in accordance with an anergy model. A homologous sequence was found between NAE 07-06 and the VDJ junction of the TCR beta-chain from an EAN 60-70-specific T cell line. Rats preimmunized with NAE 07-06 in vivo before EAN induction showed less disease severity clinically and histologically. These data suggest a new therapeutic approach for T cell-mediated autoimmune disorders through the induction of anti-TCR Abs with complementary peptide Ags.
Araga
S
S
Division of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Kishimoto
M
M
Doi
S
S
Nakashima
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D017635:Clonal Anergy / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D007106:Immune Sera / Q000378:metabolism; D007279:Injections, Subcutaneous; D018996:Myelin P2 Protein / Q000008:administration & dosage / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D007106:Immune Sera; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014614:Vaccines, Synthetic