Identification of encephalitogenic V beta-4-bearing T cells in SJL mice. Further evidence for the V region disease hypothesis?
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system mediated by T cells bearing TCR of restricted heterogeneity. Thus, in the murine PL strain, V beta-8.2 is used by 80% of the encephalitogenic T cells. This observation has led to the successful prevention and reversal of EAE by the in vivo use of mAb directed to these restricted gene products. In SJL mice, the V beta-17a gene product has been shown to be used by approximately 50% of encephalitogenic T cells subsequent to immunization with a myelin basic protein (MBP)-derived peptide. However, the other V beta genes used by encephalitogenic T cells in SJL EAE have remained uncharacterized. We now report, for the first time, the beta-chain-encoding DNA sequence of two encephalitogenic, MBP-reactive, SJL-derived T cell clones. These clones which are specific for H-2s and the carboxyl-terminus (amino acid 92-103) of MBP, use TCR encoded by V beta-4. In addition, we demonstrate that the transfer of EAE by a heterogenous SJL-derived encephalitogenic T cell line can be prevented using an anti-V beta-4 antibody in vivo. V beta-4 usage has been previously described in a H-2u/MBP amino-terminus-reactive encephalitogenic T cell. The present findings may thus further support the "V region-disease" hypothesis.
Padula
S J
SJ
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030.
Lingenheld
E G
EG
Stabach
P R
PR
Chou
C H
CH
Kono
D H
DH
Clark
R B
RB
D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell