Cutting edge: N-hydroxy peptides: a new class of TCR antagonists.
TCR antagonists are altered T cell epitopes that specifically inactivate T cells. Commonly, they are derived from agonists by amino acid side chain replacement at positions accessible to the TCR. In this paper we report for the first time that a main chain N-hydroxylation, which is not exposed at the surface of the MHC peptide complex, renders an agonist into an antagonist. These mimotopes are a new, yet undescribed class of TCR antagonists. The antagonists are about 100 times more potent than an unrelated peptide that competes for binding to the MHC molecule. The novel main chain modification enhances biostability and maintains side chain constitution and thus opens new prospects for the use of TCR antagonists in the treatment of pathological immune reactions.
Hin
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Department of Dermatology, Medical Faculty Charité, Humboldt University, Berlin, Germany.
Zabel
C
C
Bianco
A
A
Jung
G
G
Walden
P
P
D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004527:Egg Proteins / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D006183:H-2 Antigens / Q000378:metabolism; D006900:Hydroxylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*
D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C110366:OVA-8; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin