Therapeutic potential of TCR antagonists is determined by their ability to modulate a diverse repertoire of autoreactive T cells

Autor:	S M, Anderton, S, Kissler, A G, Lamont, D C, Wraith
Rok vydání:	1999
Předmět:	Encephalomyelitis Autoimmune Experimental Immunodominant Epitopes Ovalbumin T-Lymphocytes Molecular Sequence Data Receptors Antigen T-Cell Autoimmunity Mice Transgenic In Vitro Techniques Autoimmune Diseases Mice Animals Amino Acid Sequence Immunotherapy
Zdroj:	European journal of immunology. 29(6)
ISSN:	0014-2980
Popis:	The use of altered peptide ligands (APL) with TCR antagonist properties holds promise as an antigen-specific therapy for autoimmune disorders. We are investigating the therapeutic potential of APL in experimental autoimmune encephalomyelitis (EAE) using the Ac1-9 peptide of myelin basic protein in H-2u mice. Encephalitogenic T cells recognize Ac1-9 using residues 3Gln and 6Pro as the major TCR contact sites. Use of position 6 APL is compromised by the heterogeneous nature of the Ac1-9-specific repertoire. Here we identify two position 3 APL that act as TCR antagonists on transgenic T cells expressing Ac1-9-specific TCR and that inhibit EAE in H-2u mice. However, the therapeutic capacity of these two APL correlated directly with the ability to maximally inhibit activation of a heterogeneous T cell pool. The implications of these findings for the requirements for EAE induction, the relative contribution of a given T cell subpopulation to pathology and the mechanism underlying EAE inhibition in this model are discussed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::dac2b498e34a09a6cf32971f4575c139 https://pubmed.ncbi.nlm.nih.gov/10382747 Zobrazit plný text záznamu Plný text