Abstract
We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.
Original language | English (US) |
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Pages (from-to) | 2624-2634 |
Number of pages | 11 |
Journal | European Journal of Immunology |
Volume | 26 |
Issue number | 11 |
DOIs | |
State | Published - 1996 |
Externally published | Yes |
Keywords
- Altered peptide ligands
- Autoimmunity
- Human
- Myelin basic protein
- T lymphocyte
ASJC Scopus subject areas
- Immunology