HUMAN ACETYLCHOLINE-RECEPTOR PRESENTATION IN MYASTHENIA-GRAVIS - DR RESTRICTION OF AUTOIMMUNE T-EPITOPES AND BINDING OF SYNTHETIC RECEPTOR SEQUENCES TO DR MOLECULES

Autoimmune Th cells in myasthenia gravis recognize several sequence re gions of the human muscle acetylcholine receptor (AChR). Most AChR Th epitopes are presented by HLA class II DR molecules (DR). Four sequenc e regions of the AChR alpha-subunit form Th epitopes recognized by mos t myasthenic patients, irrespective of their DR haplotype. In this stu dy we first identified in five myasthenic patients the DR molecule(s) likely to be involved in presentation of T immunodominant AChR sequenc es. We then investigated the binding to the affinity purified DR molec ules thus identified (DR2/w51, DR4/w53, and DR7/w53) and to the DR1 mo lecule, of a panel of overlapping synthetic peptides screening the hum an cr-subunit sequence, previously used to identify AChR Th epitopes i n myasthenic patients. The AChR peptides that stimulated anti-AChR aut oimmune Th cells all bound the relevant DR molecules. Some AChR peptid es never recognized by Th cells of myasthenic patients also bound well to one or more DR molecules. The relative ability to bind to DR molec ules 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 uniq uely bound one DR molecule, others bound several DR molecules, and oth ers did not bind any of the DR molecules tested.