Heterogeneity of T-cell receptor usage in experimental autoimmune neuritis in the Lewis rat.
In experimental autoimmune neuritis (EAN), T-cell receptor (TCR) variable (V)-region gene usage by neuritogenic T cells has been reported to be clonally restricted at the RNA level. This study was designed to verify TCR usage by neuritogenic T cells at the protein level. We generated two monoclonal antibodies (mAbs) 7H4 and 8G8 specific for a Vbeta4/Valpha11 associated idiotype expressed by the majority of neuritogenic cells of P2-specific T-cell lines. The remaining neuritogenic P2-specific T cells either exhibited a dominant usage of the TCR Vbeta13 chain recognized by the recently generated mAbs 17D5 and 18B1 or showed diverse Vbeta usage. Treatment of adoptive-transfer (AT)-EAN or of EAN actively induced with the neuritogenic P2 peptide by mAbs 7H4 and 8G8 led to a partial, but significant, reduction of clinical disease. Treatment with Vbeta13-specific mAb 17D5 had no clear effect on active EAN. Our data show that at least three different TCR are used by P2-specific pathogenic T cells in EAN, an animal model for human inflammatory neuropathies.
Stienekemeier
M
M
Department of Neurology, Julius-Maximilians Universität, Würzburg, Germany.
Herrmann
T
T
Kruse
N
N
Weishaupt
A
A
Weilbach
F X
FX
Giegerich
G
G
Theofilopoulos
A
A
Jung
S
S
Gold
R
R
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D002460:Cell Line; D000939:Epitopes; D005260:Female; D019672:Genes, T-Cell Receptor; D018740:Genetic Heterogeneity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D011233:Precipitin Tests; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA