Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes

Dennis Bourdette, Yuan K. Chou, Ruth Whitham, Jane Buckner, Hi Jong Kwon, Gerald T. Nepom, Abigail Buenafe, Shelley A. Cooper, Mark Allegretta, George A. Hashim, Halina Offner, Arthur Vandenbark

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Abstract

Vaccination with synthetic TCR peptides from the BV5S2 complementarity- determining region 2 (CDR2) can boost significantly the frequency of circulating CD4+ peptide-specific Th2 cells in multiple sclerosis (MS) patients, with an associated decrease in the frequency of myelin basic protein (MBP)-reactive Th1 Cells and possible clinical benefit. To evaluate the immunogenicity of CDR2 vs other regions of the TCR, we vaccinated seven MS patients with overlapping BV5S2 peptides spanning amino acids 1-94. Six patients responded to at least one of three overlapping or substituted CDR2 peptides possessing a core epitope of residues 44-52, and one patient also responded to a CDR1 peptide. Of the CDR2 peptides, the substituted (Y49T)BV5S2-38-58 peptide was the most immunogenic but cross-reacted with the native sequence and had the strongest binding affinity for MS-associated HLA- DR2 alleles, suggesting that position 49 is an MHC rather than a TCR contact residue. Two MS patients who did not respond to BV5S2 peptides were immunized successfully with CDR2 peptides from different BV gene families overexpressed by their MBP-specific T cells. Taken together, these results suggest that a widely active vaccine for MS might well involve a limited set of slightly modified CDR2 peptides from BV genes involved in T cell recognition of MBP.

Original languageEnglish (US)
Pages (from-to)1034-1044
Number of pages11
JournalJournal of Immunology
Volume161
Issue number2
StatePublished - Jul 15 1998

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Complementarity Determining Regions
T-Cell Receptor Genes
T-Cell Antigen Receptor
Multiple Sclerosis
Immunity
Peptides
Myelin Basic Protein
HLA-DR2 Antigen
T-Lymphocytes
Th2 Cells
Th1 Cells
Genes
Epitopes
Vaccination
Vaccines
Alleles

ASJC Scopus subject areas

  • Immunology

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Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes. / Bourdette, Dennis; Chou, Yuan K.; Whitham, Ruth; Buckner, Jane; Kwon, Hi Jong; Nepom, Gerald T.; Buenafe, Abigail; Cooper, Shelley A.; Allegretta, Mark; Hashim, George A.; Offner, Halina; Vandenbark, Arthur.

In: Journal of Immunology, Vol. 161, No. 2, 15.07.1998, p. 1034-1044.

Research output: Contribution to journalArticle

Bourdette, Dennis ; Chou, Yuan K. ; Whitham, Ruth ; Buckner, Jane ; Kwon, Hi Jong ; Nepom, Gerald T. ; Buenafe, Abigail ; Cooper, Shelley A. ; Allegretta, Mark ; Hashim, George A. ; Offner, Halina ; Vandenbark, Arthur. / Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes. In: Journal of Immunology. 1998 ; Vol. 161, No. 2. pp. 1034-1044.
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