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 Decker, P. Articles by Muller, S. Search for Related Content PubMed PubMed Citation Articles by Decker, P. Articles by Muller, S.

Identification of a Minimal T Cell Epitope Recognized by Antinucleosome Th Cells in the C-Terminal Region of Histone H4¹

Institut de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Strasbourg, France

Autoreactive T cells responding to systemic autoantigens have been characterized in patients and mice with autoimmune diseases and in healthy individuals. Using peptides covering the whole sequence of histone H4, we characterized several epitopes recognized by lymph node Th cells from nonsystemic lupus erythematosus-prone mice immunized with the same peptides, the H4 protein, or nucleosomes. Multiple T epitopes were identified after immunizing H-2^d BALB/c mice with H4 peptides. They spanned residues 28–42, 30–47, 66–83, 72–89, and 85–102. Within the region 85–102, a minimal CD4⁺ T epitope containing residues 88–99 was characterized. Although Abs to peptide 88–99 recognized H4, this peptide does not contain a dominant B cell epitope recognized by anti-H4 Abs raised in BALB/c mice or Abs from NZB/NZW H-2^d/z lupus mice. Th cells primed in vivo with H4 responded to H4, but not to peptide 88–99. However, this peptide was able to stimulate the proliferation and IL-2 secretion of Th cells generated after immunization with nucleosomes. H4_88–99 thus represents a cryptic epitope with regard to H4 and a supradominant epitope presented by nucleosome, a supramolecular complex that plays a key role in lupus. This study shows that in the normal repertoire of naive BALB/c mice, autoreactive Th cells specific for histones are not deleted. The reactivity of these Th cells seems to be relatively restricted and resembles that of Th clones generated from SNF₁ ((SWR x NZB)F₁; I-A^d/q) lupus mice described earlier.

This article has been cited by other articles:

				H.-K. Kang, M. Liu, and S. K. Datta Low-Dose Peptide Tolerance Therapy of Lupus Generates Plasmacytoid Dendritic Cells That Cause Expansion of Autoantigen-Specific Regulatory T Cells and Contraction of Inflammatory Th17 Cells J. Immunol., June 15, 2007; 178(12): 7849 - 7858. [Abstract] [Full Text] [PDF]

				V. M. Ronnefarth, A. I. M. Erbacher, T. Lamkemeyer, J. Madlung, A. Nordheim, H.-G. Rammensee, and P. Decker TLR2/TLR4-Independent Neutrophil Activation and Recruitment upon Endocytosis of Nucleosomes Reveals a New Pathway of Innate Immunity in Systemic Lupus Erythematosus J. Immunol., December 1, 2006; 177(11): 7740 - 7749. [Abstract] [Full Text] [PDF]

				X. Chen, L. M. Reed-Loisel, L. Karlsson, and P. E. Jensen H2-O Expression in Primary Dendritic Cells J. Immunol., March 15, 2006; 176(6): 3548 - 3556. [Abstract] [Full Text] [PDF]

				M. A. Michaels, H.-K. Kang, A. Kaliyaperumal, E. Satyaraj, Y. Shi, and S. K. Datta A Defect in Deletion of Nucleosome-Specific Autoimmune T Cells in Lupus-Prone Thymus: Role of Thymic Dendritic Cells J. Immunol., November 1, 2005; 175(9): 5857 - 5865. [Abstract] [Full Text] [PDF]

				P. Decker, H. Singh-Jasuja, S. Haager, I. Kotter, and H.-G. Rammensee Nucleosome, the Main Autoantigen in Systemic Lupus Erythematosus, Induces Direct Dendritic Cell Activation via a MyD88-Independent Pathway: Consequences on Inflammation J. Immunol., March 15, 2005; 174(6): 3326 - 3334. [Abstract] [Full Text] [PDF]

				S. Fournel, S. Neichel, H. Dali, S. Farci, B. Maillere, J.-P. Briand, and S. Muller CD4+ T Cells from (New Zealand Black x New Zealand White)F1 Lupus Mice and Normal Mice Immunized Against Apoptotic Nucleosomes Recognize Similar Th Cell Epitopes in the C Terminus of Histone H3 J. Immunol., July 15, 2003; 171(2): 636 - 644. [Abstract] [Full Text] [PDF]

				H. Dumortier, F. Monneaux, B. Jahn-Schmid, J.-P. Briand, K. Skriner, P. L. Cohen, J. S. Smolen, G. Steiner, and S. Muller B and T Cell Responses to the Spliceosomal Heterogeneous Nuclear Ribonucleoproteins A2 and B1 in Normal and Lupus Mice J. Immunol., August 15, 2000; 165(4): 2297 - 2305. [Abstract] [Full Text] [PDF]