T cell recognition motifs of an immunodominant peptide of myelin basic protein in patients with multiple sclerosis: structural requirements and clinical implications
In: European Journal of Immunology, Jg. 28 (1998-06-01), S. 1894-1901
Online
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Zugriff:
Myelin basic protein (MBP)-reactive T cells may play an important role in the pathogenesis of multiple sclerosis (MS). The T cell response to the 83-99 region of MBP represents a dominant autoreactive response to MBP in MS patients of DR2 haplotype. In this study, a large panel of DR2- and DR4-restricted T cell clones specific for the MBP83-99 peptide were examined for the recognition motifs and structural requirements for antigen recognition using alanine-substituted peptides. Our study revealed that although the recognition motifs of the T cell clones were diverse, the TCR contact residues within the 83-99 region of MBP were highly conserved. Two central residues (Phe90 and Lys91) served as the critical TCR contact points for both DR2- and DR4-restricted T cell clones. Single alanine substitution at residue 90 or residue 91 abolished the responses of 81-95 % of the T cell clones while a double alanine substitution rendered all T cell clones unresponsive. It was also demonstrated in this study that the substituted peptides altered the cytokine profile of some, but not all, T cell clones. Some MBP83-99-specific T cell clones were able to sustain alanine substitutions and were susceptible to activation by microbial antigens. The study has an important implication in designing a peptide-based therapy for MS.
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T cell recognition motifs of an immunodominant peptide of myelin basic protein in patients with multiple sclerosis: structural requirements and clinical implications
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Autor/in / Beteiligte Person: | Lnu, Savita ; Rivera, Victor M. ; Boehme, Stefen A. ; Aebischer, Iwan ; Zhang, Jingwu Z. ; Crowe, Paul D. ; Kozovska, Milena ; Zang, Ying C. Q. |
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Zeitschrift: | European Journal of Immunology, Jg. 28 (1998-06-01), S. 1894-1901 |
Veröffentlichung: | Wiley, 1998 |
Medientyp: | unknown |
ISSN: | 1521-4141 (print) ; 0014-2980 (print) |
DOI: | 10.1002/(sici)1521-4141(199806)28:06<1894::aid-immu1894>3.0.co;2-w |
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