Persistent expression of experimental autoimmune encephalomyelitis (EAE)-specific Vbeta8.2 TCR spectratype in the central nervous system of rats with chronic relapsing EAE.
Monitoring the TCR repertoire is indispensable for the assessment of T cell-associated autoimmune diseases and subsequent TCR-based immunotherapy. In the present study, we examined the TCR repertoire of spinal cord T cells of Lewis rats by CDR3 spectratyping during chronic relapsing experimental autoimmune encephalomyelitis (EAE) induced by immunization with spinal cord homogenate. It was found that Vbeta8.2 spectratype with the shortest CDR3 expanded oligoclonally throughout the course of the disease. In addition, Vbeta12 spectratype expansion was observed at the first and second attacks of EAE. Sequence analysis revealed that clones with the DSSYEQYF sequence, which is a representative sequence of myelin basic protein (MBP)-reactive T cell clones, constituted the predominant population in the Vbeta8.2 family. Surprisingly, Vbeta12 also used the identical amino acid sequence in the CDR3 region. These findings indicate that although infiltrating T cells in the central nervous system are activated polyclonally, the TCR repertoire remains unchanged throughout the course. Moreover, the finding that the predominant CDR3 amino acid sequence of Vbeta8.2 and Vbeta12 spectratypes is identical with that of MBP-induced EAE suggests that a single Ag in spinal cord homogenate, possibly MBP, is involved in disease development.
Kim
G
G
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Japan.
Kohyama
K
K
Tanuma
N
N
Arimito
H
H
Matsumoto
Y
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006168:Guinea Pigs; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012008:Recurrence; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta