Human acetylcholine receptor presentation in myasthenia gravis: DR restriction of autoimmune T epitopes and binding of synthetic receptor sequences to DR molecules

Angelo A. Manfredi, Mi Ha Yuen, Lucia Moiola, Maria Pia Protti, Bianca M. Conti-Tronconi

Research output: Contribution to journalArticlepeer-review

Abstract

Autoimmune Th cells in myasthenia gravis recognize several sequence regions of the human muscle acetylcholine receptor (AChR). Most AChR Th epitopes are presented by HLA class II DR molecules (DR). Four sequence regions of the AChR α-subunit form Th epitopes recognized by most myasthenic patients, irrespective of their DR haplotype. In this study, we first identified in five myasthenic patients the DR molecule(s) likely to be involved in presentation of T immunodominant AChR sequences. We then investigated the binding to the affinity purified DR molecules thus identified (DR2/w51, DR4/w53, and DR7/w53) and to the DR1 molecule, of a panel of overlapping synthetic peptides screening the human α-subunit sequence, previously used to identify AChR Th epitopes in myasthenic patients. The AChR peptides that stimulated anti-AChR autoimmune Th cells all bound the relevant DR molecules. Some AChR peptides never recognized by Th cells of myasthenic patients also bound well to one or more DR molecules. The relative ability to bind to DR molecules of different sequence regions of the AChR, i.e., an autoantigen, agrees well with the results of previous studies on the DR binding of synthetic sequences of exogenous antigens. Some peptide sequences uniquely bound one DR molecule, others bound several DR molecules, and others did not bind any of the DR molecules tested.

Original languageEnglish
Pages (from-to)4165-4174
Number of pages10
JournalJournal of Immunology
Volume152
Issue number8
Publication statusPublished - Apr 15 1994

ASJC Scopus subject areas

  • Immunology

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