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Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.

Abstract
Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.
AuthorsC Gelber, L Gemmell, D McAteer, M Homola, P Swain, A Liu, K J Wilson, M Gefter
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 158 Issue 5 Pg. 2425-34 (Mar 1 1997) ISSN: 0022-1767 [Print] UNITED STATES
PMID9036993 (Publication Type: Journal Article)
Chemical References
  • Carrier Proteins
  • Catechols
  • Haptens
  • Histocompatibility Antigens Class II
  • Interleukin-2
  • Peptides
  • Trinitrobenzenes
  • 3-pentadecacatechol
Topics
  • Administration, Topical
  • Animals
  • Carrier Proteins (chemical synthesis, chemistry, therapeutic use)
  • Catechols (administration & dosage, chemical synthesis, chemistry)
  • Dermatitis, Toxicodendron (immunology, prevention & control)
  • Down-Regulation (immunology)
  • Haptens (immunology, therapeutic use)
  • Histocompatibility Antigens Class II (metabolism)
  • Immune Tolerance (drug effects)
  • Interleukin-2 (secretion)
  • Lymphocyte Activation (drug effects)
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Peptides (metabolism, physiology)
  • Protein Binding (drug effects, immunology)
  • Skin (immunology)
  • T-Lymphocytes (immunology, metabolism)
  • Trinitrobenzenes (immunology, therapeutic use)

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