The Journal of Immunology, Vol 158, Issue 2 591-597, Copyright © 1997 by American Association of Immunologists

ARTICLES

Carrier-independent hapten recognition and promiscuous MHC restriction by CD4 T cells induced by trinitrophenylated peptides

J Kohler, U Hartmann, R Grimm, U Pflugfelder and HU Weltzien
Max Planck Institute of Immunobiology, Freiburg, Germany.

The elucidation of mechanisms underlying the recognition of haptens by class II MHC-restricted T cells is instrumental for the understanding of chemical- and drug-induced allergies. We have previously demonstrated that trinitrophenyl (TNP) peptides represent dominant antigenic epitopes for CD8+ and CD4+ mouse T cells triggered by chemically TNP-modified APC. Here, we report the characterization of TNP-specific, CD4+ mouse T cell lines and hybridomas that were induced in vivo and in vitro by defined hapten-conjugated peptides. These peptides, which we had previously shown to induce contact sensitivity to picryl chloride in vivo regardless of sequence homologies to mouse proteins, were found to activate carrier-independent TNP-specific T cells in vitro. We interpret these findings to support our view that carrier-independent T cells, reactive to particularly repetitive hapten epitopes, may play a crucial role in allergies to chemicals and drugs. In addition to carrier independence, one of our hybridomas (IT-H6/A11) exhibited a striking promiscuity of MHC restriction. Although absolutely dependent in its TNP reactivity on the presence of MHC class II molecules, the IT H6/A11 hybridoma completely ignored class II polymorphism and even reacted to TNP peptides presented on human DR molecules. Regarding hapten allergies in humans with a heterozygous situation for three types of class II molecules (DR, DP, and DQ), such promiscuous MHC restriction should lead to the presentation of even higher epitope densities to the respective T cell clones. Hybridoma IT- H6/A11, reacting to TNP independent of carrier peptide and of MHC haplotype, also allowed for an unusually systematic study of the minimal requirements for TNP recognition. Despite an almost complete ignorance of amino acid side chains on the carrier peptide, our data indicate a clearly position-specific interaction of hapten and TCR.

This article has been cited by other articles:

				S. F. Martin, J. C. Dudda, V. Delattre, E. Bachtanian, C. Leicht, B. Burger, H. U. Weltzien, and J. C. Simon Fas-Mediated Inhibition of CD4+ T Cell Priming Results in Dominance of Type 1 CD8+ T Cells in the Immune Response to the Contact Sensitizer Trinitrophenyl J. Immunol., September 1, 2004; 173(5): 3178 - 3185. [Abstract] [Full Text] [PDF]

				J. Stockl, O. Majdic, G. Fischer, D. Maurer, and W. Knapp Monomorphic Molecules Function as Additional Recognition Structures on Haptenated Target Cells for HLA-A1-Restricted, Hapten-Specific CTL J. Immunol., September 1, 2001; 167(5): 2724 - 2733. [Abstract] [Full Text] [PDF]

				S. von Greyerz, G. Bultemann, K. Schnyder, C. Burkhart, B. Lotti, Y. Hari, and W. J. Pichler Degeneracy and additional alloreactivity of drug-specific human {{alpha}}{beta}+ T cell clones Int. Immunol., July 1, 2001; 13(7): 877 - 885. [Abstract] [Full Text] [PDF]

				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]

				W. J Pichler and N. Yawalkar Allergic reactions to drugs: involvement of T cells Thorax, October 1, 2000; 55(90002): 61S - 65. [Full Text]

				A. Franco, T. Yokoyama, D. Huynh, C. Thomson, S. G. Nathenson, and H. M. Grey Fine Specificity and MHC Restriction of Trinitrophenyl- Specific CTL J. Immunol., March 15, 1999; 162(6): 3388 - 3394. [Abstract] [Full Text] [PDF]

				B. Kessler, O. Michielin, C. L. Blanchard, I. Apostolou, C. Delarbre, G. Gachelin, C. Gregoire, B. Malissen, J.-C. Cerottini, F. Wurm, et al. T Cell Recognition of Hapten. ANATOMY OF T CELL RECEPTOR BINDING OF A H-2Kd-ASSOCIATED PHOTOREACTIVE PEPTIDE DERIVATIVE J. Biol. Chem., February 5, 1999; 274(6): 3622 - 3631. [Abstract] [Full Text] [PDF]