Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention.
Experimental allergic encephalomyelitis (EAE) is an induced autoimmune disease mediated by CD4+ T lymphocytes. Analysis of T cell receptors of myelin basic protein-specific encephalitogenic T cell clones derived from six different PL/J (H-2u) or (PL/J x SJL) F1 (H-2uxs) mice revealed a limited heterogeneity in primary structure. In vivo, the majority of T lymphocytes recognize the N-terminal MBP-nonapeptide in association with I-Au and utilize the V beta 8 gene element. cDNA-sequencing showed that all T cell receptors from a panel of such T cell clones, grown in vitro, share the same V alpha gene segment. Despite heterogeneity in the D-J regions, the clones unexpectedly display a striking similarity in fine specificity. Based on these results, prevention and reversal of autoimmune disease with V beta 8-specific monoclonal antibodies was achieved.
Acha-Orbea
H
H
Department of Medical Microbiology, Stanford University School of Medicine, California 94305.
Mitchell
D J
DJ
Timmermann
L
L
Wraith
D C
DC
Tausch
G S
GS
Waldor
M K
MK
Zamvil
S S
SS
McDevitt
H O
HO
Steinman
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D001483:Base Sequence; D002999:Clone Cells; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D000939:Epitopes / Q000032:analysis; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011897:Random Allocation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell