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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by den Haan, J. M. M. Articles by Goulmy, E. Search for Related Content PubMed PubMed Citation Articles by den Haan, J. M. M. Articles by Goulmy, E. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2002, Vol. 99, No. 3, pp. 985-992 IMMUNOBIOLOGY General T-cell receptor antagonists to immunomodulate HLA-A2-restricted minor histocompatibility antigen HA-1-specific T-cell responses Joke M. M. den Haan, Tuna Mutis, Els Blokland, Ad P. IJzerman, and Els Goulmy From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, and the Department of Medicinal Chemistry, Leiden University, Leiden/Amsterdam Center for Drug Research, The Netherlands. T-cell receptors (TCRs) of a series of minor histocompatibility antigen (mHag) HA-1-specific cytotoxic T-cell (CTL) clones isolated from 3 unrelated patients have been shown to use the same BV6S4A2 segment with conserved amino acids in the CDR3V region. This suggests that different HA-1-specific TCRs interact similarly to the HA-1 antigen presented by the HLA-A2 molecule. The mHag HA-1 forms an immunogenic complex with HLA-A2 and induces strong alloimmune responses after stem cell transplantation (SCT). It was questioned, therefore, whether clonal and polyclonal HA-1-specific CTL responses can be antagonized by a single TCR antagonistic peptide. Functional analysis and molecular modeling of single and double amino acid substitutions of TCR contact residues, adjacent residues, and HLA-A2 binding residues resulted in 4 peptides with high affinity for HLA-A2 and with the capacity to inhibit the lysis of endogenously HA-1-expressing EBV-BLCL by 3 different HA-1-specific CTL clones. These peptides also efficiently antagonized HA-1-specific polyclonal CTL lines derived from 3 patients and significantly reduced the number of interferon--producing HA-1-specific CTL of a patient with graft-versus-host disease after HA-1-mismatched SCT. These data show that general TCR antagonists can be developed that inhibit HLA-A2-restricted HA-1-specific CTL responses on the clonal and the polyclonal level and that TCR antagonists may modulate the immunodominant mHag HA-1 responses. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Spierings, S. Gras, J.-B. Reiser, B. Mommaas, M. Almekinders, M. G. D. Kester, A. Chouquet, M. Le Gorrec, J. W. Drijfhout, F. Ossendorp, et al. Steric Hindrance and Fast Dissociation Explain the Lack of Immunogenicity of the Minor Histocompatibility HA-1Arg Null Allele J. Immunol., April 15, 2009; 182(8): 4809 - 4816. [Abstract] [Full Text] [PDF] S. Nicholls, K. P. Piper, F. Mohammed, T. R. Dafforn, S. Tenzer, M. Salim, P. Mahendra, C. Craddock, P. van Endert, H. Schild, et al. Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition PNAS, March 10, 2009; 106(10): 3889 - 3894. [Abstract] [Full Text] [PDF] A. J. Barrett, K. Rezvani, S. Solomon, A. M. Dickinson, X. N. Wang, G. Stark, H. Cullup, M. Jarvis, P. G. Middleton, and N. Chao New Developments in Allotransplant Immunology Hematology, January 1, 2003; 2003(1): 350 - 371. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020