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J. Exp. Med.,
Volume 187, Number 12, June 15, 1998 2055-2063
By
From the Institute of Pathology, Case Western Reserve University, School of Medicine, Cleveland,
Ohio 44106
To study the contribution of endogenous myelin basic protein (MBP) to the positive and/or
negative selection of the MBP-specific T cell repertoire, we studied the T cell response to
MBP in MBP-deficient shiverer and MBP-expressing congenic C3H mice. Immunization
with MBP induced a vigorous T cell response in shiverer mice directed against a single I-Ak-
restricted immunodominant determinant, the core of which is peptide MBP:79-87 (DENPVVHFF). Injection of this peptide induced a high avidity T cell repertoire in shiverer mice that
primarily consisted of clones capable of recognizing the native MBP protein in addition to the
peptide itself. These data show that endogenous MBP is not required for the positive selection
of an MBP-specific T cell repertoire. C3H mice, in contrast, were selectively unresponsive to
the MBP protein and injection of MBP:79-87 peptide induced a low avidity repertoire that
could be stimulated only by the peptide, not by the protein. Therefore, endogenous MBP induced profound inactivation of high avidity clones specific for the immunodominant determinant making that determinant appear cryptic.
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