HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bourdette, D. N. Articles by Vandenbark, A. A. Search for Related Content PubMed PubMed Citation Articles by Bourdette, D. N. Articles by Vandenbark, A. A.

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*^{1 ,2}

Dennis N. Bourdette^*,,, Yuan K. Chou^,, Ruth H. Whitham^*,,, Jane Buckner^§, Hi Jong Kwon^¶, Gerald T. Nepom^§, Abigail Buenafe^,, Shelley A. Cooper, Mark Allegretta^||, George A. Hashim^#, Halina Offner^, and Arthur A. Vandenbark^3,,,**

^* Neurology Service, and Research Service, Veterans Affairs Medical Center, Portland, OR 97207; Department of Neurology, Oregon Health Sciences University, Portland, OR 97201; ^§ Virginia Mason Research Center, Seattle, WA 98101 and the Departments of Rheumatology and Immunology, University of Washington, Seattle, WA 98195; ^¶ Department of Clinical Pathology, St. Paul’s Hospital, Seoul, Korea; ^|| Connetics Corporation, Palo Alto, CA 94303; ^# Council for Tobacco Research, New York, NY 10022; and ^** Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201

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.

This article has been cited by other articles:

				D N Bourdette, E Edmonds, C Smith, J D Bowen, C R. Guttmann, Z P Nagy, J Simon, R Whitham, J Lovera, V Yadav, et al. A highly immunogenic trivalent T cell receptor peptide vaccine for multiple sclerosis Multiple Sclerosis, October 1, 2005; 11(5): 552 - 561. [Abstract] [PDF]

				E. A. E. van Tienhoven, C. P. M. Broeren, A. Noordzij, J. P. A. Wagenaar, W. van Eden, and M. H. M. Wauben Nasal application of a naturally processed and presented T cell epitope derived from TCR AV11 protects against adjuvant arthritis Int. Immunol., December 1, 2000; 12(12): 1715 - 1721. [Abstract] [Full Text] [PDF]

				R N S Heard, S M Teutsch, B H Bennetts, S D Lee, E M Deane, and G J Stewart Lack of restriction of T cell receptor beta variable gene usage in cerebrospinal fluid lymphocytes in acute optic neuritis J. Neurol. Neurosurg. Psychiatry, November 1, 1999; 67(5): 585 - 590. [Abstract] [Full Text]