scholarly journals Endogenous Myelin Basic Protein Inactivates the High Avidity T Cell Repertoire

1998 ◽  
Vol 187 (12) ◽  
pp. 2055-2063 ◽  
Author(s):  
Oleg S. Targoni ◽  
Paul V. Lehmann
Keyword(s):  
T Cell ◽  
Myelin Basic Protein ◽  
Cell Response ◽  
Basic Protein ◽  
T Cell Response ◽  
High Avidity ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
C3h Mice ◽  
Selection Of

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.

Myelin basic protein and myelin oligodendrocyte glycoprotein T-cell repertoire in childhood and juvenile multiple sclerosis

2006 ◽  
Vol 12 (4) ◽  
pp. 412-420 ◽  
Author(s):  
Jorge Correale ◽  
Silvia N Tenembaum
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
T Cell Repertoire ◽  
Adult Onset ◽  
Cell Repertoire ◽  
Juvenile Onset ◽  
Exon 2

Multiple sclerosis (MS) is usually a disease of young adulthood, its clinical onset occurring between 20 and 40 years of age; however, today there is general consensus that MS can also occur in children, adolescents and even in infants. In order to gain further insight into the T-cell repertoire present in this particular group of patients myelin basic protein (MBP)-, MBP exon-2- and myelin oligodendrocyte glycoprotein (MOG)Igd-specific T-cell lines (TCLs) were isolated from 18 patients whose symptoms had started before the age of 16. Epitope specificity was established by measuring proliferative responses, and interferon-g (IFN-g) secretion by using a panel of overlapping synthetic peptides. For MOGIgd, the T-cell response was focused on three main immunodominant epitopes comprising residues 1-26, 36-60 and 63-87. For MBP the predominant immune responses were directed against peptides 83-102, 139-153 and 146-162. When compared to those observed in adult-onset MS patients, anti-MOGIgd specificity and anti-MBP responses showed similar results. Moreover, the number of MBP exon-2 TCLs isolated, and the magnitude of the specific IFN-g secretion induced were similar, both in childhood/juvenile-onset and adult-onset MS patients. Thus, despite differences in the clinical and neuroimaging manifestations of MS, these results would seem to indicate that both the spectrum of MBP found, as well as the MOGIgd epitopes recognized by peripheral blood T cells in MS, appear to be similar for childhood/juvenile-onset and adult-onset patients.

Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD): evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 868-876 ◽  
Author(s):  
Yuji Miura ◽  
Christopher J. Thoburn ◽  
Emilie C. Bright ◽  
Matthias Sommer ◽  
Susan Lefell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Graft Versus Host Disease ◽  
Cell Response ◽  
Effector T Cells ◽  
T Cell Response ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Graft Versus Host

Abstract Administration of cyclosporine A (CsA) after autologous stem cell transplantation elicits an autoimmune syndrome with pathology similar to graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with the appearance of autoreactive T cells directed at major histocompatibility class (MHC) class II antigens. In the rat model of autologous GVHD, clonal analysis reveals that the effector T cells are highly conserved and recognize a peptide from the invariant chain peptide presented by MHC class II. Although human autologous GVHD effector T cells share a similar phenotypic specificity, clonality of the response in humans has not been determined. To examine the human effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes was assessed by complementarity-determining region 3 (CDR3) size distribution analysis and T-cell clonotype analysis in 26 patients treated with CsA after transplantation. Autologous GVHD developed in 3 of 4 patients with human leukocyte antigen (HLA)-DRB1*0701, and clonal expansions of β-chain variable region (BV)16+ T cells were shared. Clonal expansions within BV15+ and BV22+ T cells were also detected in 4 of 6 patients with HLA-DRB1*1501 and in 3 of 4 patients with HLA-DRB1*0401, respectively. Sequencing of BV16 cDNA for which the CDR3 size pattern exhibited apparent clone predominance revealed an identical CDR3 peptide sequence in 2 different patients, one with HLA-DRB1*0701 and the other with HLA-DRB1*1502. These findings indicate that the discrete antigen-driven expansion of T cells is involved in autologous GVHD.

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