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 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.
Targoni
O S
OS
Institute of Pathology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
Lehmann
P V
PV
D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D017951:Antigen Presentation; D018604:Epitope Mapping; D015321:Gene Rearrangement; D016056:Immunodominant Epitopes; D007156:Immunologic Memory; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C112836:myelin basic protein 79-87