Cross-reactivity of T-cell clones specific for altered peptide ligands of myelin basic protein
| Autor: | Katarzyna D. Bieganowska, David A. Hafler, Lara J. Ausubel |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
T cell
Receptors Antigen T-Cell alpha-beta T-Lymphocytes Immunology Population Molecular Sequence Data Peptide Cross Reactions Cell Line Antigen medicine Humans Amino Acid Sequence education Receptor Peptide sequence chemistry.chemical_classification education.field_of_study biology T-cell receptor Myelin Basic Protein Molecular biology Peptide Fragments Myelin basic protein medicine.anatomical_structure chemistry biology.protein |
| Zdroj: | Cellular immunology. 193(1) |
| ISSN: | 0008-8749 |
| Popis: | We have determined that certain altered peptide ligands (APLs) can induce T-cells specific for the native peptide myelin basic protein (MBP) p85-99 to secrete Th2-type cytokines such as IL-4 and IL-5 in the absence of significant Th1-type cytokines. However, it is not known whether stimulation with APLs will activate autoreactive T cells or a distinct population of cells. In the present study, 18 T-cell clones that reacted with either MBP p85-99 or one of three APLs of the peptide substituted at TCR contact residues were generated. T-cells were tested functionally for their reactivity to the original stimulating peptide as well as to the MBP APLs. In addition, the T-cell receptor (TCR) alpha and beta chains of each of these clones were sequenced. In a series of T-cell clones isolated from a multiple sclerosis patient, stimulation of T-cells with the APL 93A, which has an alanine for lysine substitution at the TCR contact residue 93, did not induce substantial proliferation of MBPp85-99-specific T-cell clones, indicating that a distinct set of T-cell clones was induced. However, this was not the case for another set of T-cell clones from a different individual in which the 93A peptide induced clonal expansion of T-cells highly reactive with the native MBPp85-99 antigen. Thus, the potential beneficial effect of using APLs to induce downregulatory cytokines appears to depend on the specific T-cell repertoire of the individual patient. |
| Databáze: | OpenAIRE |
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