Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention

H Acha-Orbea, DJ Mitchell, L Timmermann, DC Wraith… - Cell, 1988 - cell.com
H Acha-Orbea, DJ Mitchell, L Timmermann, DC Wraith, GS Tausch, MK Waldor, SS Zamvil
Cell, 1988cell.com
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 PLN (H-2”) or (PL/J x SJL) Fl (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 VB8 gene element. cDNA-sequencing showed that all T cell receptors from a panel of …
Summary
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 PLN (H-2”) or (PL/J x SJL) Fl (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 VB8 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, gene segment. Despite heterogeneity in the DJ regions, the clones unexpectedly display a striking similarity in fine specificity, Based on these results, prevention and reversal of autoimmune disease with VB8-specific monoclonal antibodies was achieved.
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