DIFFERENTIAL RECOGNITION OF MBP EPITOPES IN BALB C MICE DETERMINES THE SITE OF INFLAMMATORY DISEASE INDUCTION/

Although myelin basic protein (MBP)-recognizing T cells are not readil y obtained after immunization of BALB/c mice with MBP (reflecting the BALB/c resistance to actively induced experimental autoimmune encephal omyelitis (EAE)), they can be expanded and cloned after several rounds of in vitro culture. The majority of BALB/c-derived clones recognize an epitope defined by MBP peptide 59-76. When transferred to naive BAL B/c recipients, these clones cause classical EAE, with characteristic inflammation and demyelination of the central nervous system (CNS). We previously showed that two related clones recognizing a minor epitope , defined by MBP peptide 151-168, cause inflammation and demyelination preferentially of the peripheral nervous system (PNS). Because MBP ha s alternatively spliced isoforms, residues 151-168 are not present con tiguously in all MBP isoforms. In order to determine whether induction of PNS disease is idiosyncratic to these sister clones, or related to their properties of epitope recognition, an independent T-cell line w ith similar recognition properties was studied. Clone 116F, derived fr om a BALB/c shiverer mouse, expresses a different T-cell receptor (TCR ), with distinct TCR contact residues, but like the previously describ ed T cells, this clone requires residues from both exons 6 and 7 for o ptimal stimulation. When adoptively transferred to BALB/c recipients, this clone preferentially induces disease of the PNS. A control BALB/c shiverer-derived MBP 59-76-recognizing clone, in contrast induces CNS disease. These data strongly suggest that the site of disease initiat ion may correlate with epitope recognition, particularly when alternat ive isoforms are involved. (C) 1998 Elsevier Science B.V. All rights r eserved.