Characterization of T cell receptor associated with the development of P2 peptide-induced autoimmune neuritis.
To characterize experimental autoimmune neuritis (EAN)-inducing T cells in more detail, we performed CDR3 spectratyping analysis and found oligoclonal expansion of several Vbeta spectratypes in nerve-infiltrating T cells. Vbeta5 expansion was observed all the stages examined, whereas Vbeta8.2 and Vbeta17 expansion was mainly found at the peak and preclinical stages, respectively. Since Vbeta5 expansion persists throughout the course of the disease, Vbeta5+ T cells are judged to be the main effector cells. Vbeta8.2+ and Vbeta17+ T cells may also be pathogenic but are not the main effectors because expansion of these spectratypes was found at a limited period of time. Sequence analysis revealed that Vbeta5, Vbeta8.2 and Vbeta17 spectratype-derived TCR clones possess their own dominant sequences in the CDR3 region with no homology among the clones. These findings suggest that polyclonally activated T cells are involved in the formation of the nerve lesion. Furthermore, vaccination with Vbeta5 DNA, but not with Vbeta10 DNA, suppressed the development of EAN significantly. Collectively, these findings indicate that determination of autoimmune disease-associated TCR by CDR3 spectratyping provides useful information for designing TCR-based immunotherapy for the disease.
Matsumoto
Y
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan. matyoh@tmin.ac.jp
Kim
G
G
Tanuma
N
N
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D008969:Molecular Sequence Data; D018996:Myelin P2 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use
D018996:Myelin P2 Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019444:Vaccines, DNA; C403271:myelin P2 protein (53-78)