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 Vollmer, J. Articles by Moulon, C. Search for Related Content PubMed PubMed Citation Articles by Vollmer, J. Articles by Moulon, C.

TCR Reactivity in Human Nickel Allergy Indicates Contacts with Complementarity-Determining Region 3 but Excludes Superantigen-Like Recognition¹

Jörg Vollmer^2,*,, Hans Ulrich Weltzien^3,* and Corinne Moulon^4,*

^* Max-Planck-Institut für Immunbiologie, Freiburg, Germany; and Fakultät für Biologie, Universität Freiburg, Freiburg, Germany

Nickel is the most common inducer of contact sensitivity in humans. We previously found that overrepresentation of the TCRBV17 element in Ni-induced CD4⁺ T cell lines of Ni-allergic patients relates to the severity of the disease. Amino acid sequences of these ß-chains suggested hypothetical contact points for Ni²⁺ ions in complementarity-determining region (CDR) 1 and CDR3. To specifically address the molecular requirements for Ni recognition by TCR, human TCR - and ß-chains of VB17⁺ Ni-reactive T cell clones were functionally expressed together with the human CD4 coreceptor in a mouse T cell hybridoma. Loss of CD4 revealed complete CD4 independence for one of the TCR studied. Putative TCR/Ni contact points were tested by pairing of TCR chains from different clones, also with different specificity. TCRBV17 chains with different J regions, but similar CDR3 regions, could be functionally exchanged. Larger differences in the CDR3 region were not tolerated. Specific combinations of - and ß-chains were required, excluding a superantigen-like activation by Ni. Mutation of amino acids in CDR1 of TCRBV17 did not affect Ag recognition, superantigen activation, or HLA restriction. In contrast, mutation of Arg⁹⁵ or Asp⁹⁶, conserved in many CDR3B sequences of Ni-specific, VB17⁺ TCR, abrogated Ni recognition. These results define specific amino acids in the CDR3B region of a VB17⁺ TCR to be crucial for human nickel recognition. CD4 independence implies a high affinity of such receptor types for the Ni/MHC complex. This may point to a dominant role of T cells bearing such receptors in the pathology of contact dermatitis.

This article has been cited by other articles:

				H.-J. Thierse, C. Moulon, Y. Allespach, B. Zimmermann, A. Doetze, S. Kuppig, D. Wild, F. Herberg, and H. U. Weltzien Metal-Protein Complex-Mediated Transport and Delivery of Ni2+ to TCR/MHC Contact Sites in Nickel-Specific Human T Cell Activation J. Immunol., February 1, 2004; 172(3): 1926 - 1934. [Abstract] [Full Text] [PDF]

				K. Dornmair, N. Goebels, H.-U. Weltzien, H. Wekerle, and R. Hohlfeld T-Cell-Mediated Autoimmunity: Novel Techniques to Characterize Autoreactive T-Cell Receptors Am. J. Pathol., October 1, 2003; 163(4): 1215 - 1226. [Abstract] [Full Text] [PDF]

				K. Gamerdinger, C. Moulon, D. R. Karp, J. van Bergen, F. Koning, D. Wild, U. Pflugfelder, and H. U. Weltzien A New Type of Metal Recognition by Human T Cells: Contact Residues for Peptide-independent Bridging of T Cell Receptor and Major Histocompatibility Complex by Nickel J. Exp. Med., May 19, 2003; 197(10): 1345 - 1353. [Abstract] [Full Text] [PDF]

				J. Loh and J. Fraser Metal-derivatized Major Histocompatibility Complex: Zeroing in on Contact Hypersensitivity J. Exp. Med., March 3, 2003; 197(5): 549 - 552. [Full Text] [PDF]

				L. Lu, J. Vollmer, C. Moulon, H. U. Weltzien, P. Marrack, and J. Kappler Components of the Ligand for a Ni++ Reactive Human T Cell Clone J. Exp. Med., March 3, 2003; 197(5): 567 - 574. [Abstract] [Full Text] [PDF]

				L. Budinger, N. Neuser, U. Totzke, H. F. Merk, and M. Hertl Preferential Usage of TCR-V{beta}17 by Peripheral and Cutaneous T Cells in Nickel-Induced Contact Dermatitis J. Immunol., November 15, 2001; 167(10): 6038 - 6044. [Abstract] [Full Text] [PDF]

				S. Honda, W. Zhang, A. M. Kalergis, T. P. DiLorenzo, F. Wang, and S. G. Nathenson Hapten Addition to an MHC Class I-Binding Peptide Causes Substantial Adjustments of the TCR Structure of the Responding CD8+ T Cells J. Immunol., October 15, 2001; 167(8): 4276 - 4285. [Abstract] [Full Text] [PDF]

				N. Hallab, K. Merritt, and J. J. Jacobs Metal Sensitivity in Patients with Orthopaedic Implants J. Bone Joint Surg. Am., March 1, 2001; 83(3): 428 - 428. [Full Text]

				J. Vollmer, H. U. Weltzien, K. Gamerdinger, S. Lang, Y. Choleva, and C. Moulon Antigen contacts by Ni-reactive TCR: typical {alpha}{beta} chain cooperation versus {alpha} chain-dominated specificity Int. Immunol., December 1, 2000; 12(12): 1723 - 1731. [Abstract] [Full Text] [PDF]

				B. L. Kotzin, M. T. Falta, F. Crawford, E. F. Rosloniec, J. Bill, P. Marrack, and J. Kappler Use of soluble peptide-DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis PNAS, January 4, 2000; 97(1): 291 - 296. [Abstract] [Full Text] [PDF]