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© The Rockefeller University Press, 0022-1007/1998/6/2055/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 12, June 15, 1998 2055-2063

Articles

Endogenous Myelin Basic Protein Inactivates the High Avidity T Cell Repertoire

Oleg S. Targoni and Paul V. Lehmann

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.

Key Words: cryptic determinant • T cell tolerance • MBP-specific repertoire • T cell affinity • determinant hierarchy

Address correspondence to Paul V. Lehmann, Case Western Reserve University, Department of Pathology, BRB 929, 10900 Euclid Ave., Cleveland, OH 44106-4943. Phone: 216-368-1297; Fax: 216-368-1357; E-mail: pvl2{at}po.cwru.edu

The work was supported by research grants 2470 A-1/2 from the National Multiple Sclerosis Society, 194150 from the Juvenile Diabetes Foundation, NIDDK DK-48799 and AI 42635-01 from the National Institutes of Health, and by developmental funds from the CWRU Skin Disease Research Center (AR-39750-08).

Abbreviations used: CNS, central nervous system; EAE, experimental allergic encephalomyelitis; HEL, hen eggwhite lysozyme; MBP, myelin basic protein; gpMBP, guinea pig MBP; mMBP, mouse MBP.


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