ENDOGENOUS MYELIN BASIC-PROTEIN INACTIVATES THE HIGH AVIDITY T-CELL REPERTOIRE

To study the contribution of endogenous myelin basic protein (MBP) to the positive and/or negative selection of the MBP-specific T cell repe rtoire, we studied the T cell response to MBP in MBP-deficient shivere r and MBP-expressing congenic C3H mice. Immunization with MBP induced a vigorous T cell response in shiverer mice directed against a single I-A(k)-restricted immunodominant determinant, the cope of which is pep tide MBP:79-87 (DENPV-VHFF). 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 t he 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 an d injection of MBP:79-87 peptide induced a low avidity repertoire that could be stimulated only by the peptide, not by the protein. Therefor e, endogenous MBP induced profound inactivation of high avidity clones specific for the immunodominant determinant making that determinant a ppear cryptic.