BINDING OF PEPTIDES OF THE HUMAN ACETYLCHOLINE-RECEPTOR ALPHA-SUBUNITTO HLA CLASS-II OF PATIENTS WITH MYASTHENIA-GRAVIS

MG is an autoimmune disease in which T cells specific to T-cell epitop es of the human acetylcholine receptor play a role. We have identified two peptides, p195-212 and p259-271, of the human acetylcholine recep tor alpha-subunit, to which PBLs of MG patients responded by prolifera tion. Nevertheless, proliferation assays are relatively complicated to perform and might be affected by medications taken by the patients. T herefore, we tested the possibility of using a different assay to dete rmine recognition of these peptides by MG patients. Thus, we performed a direct binding assay using biotinylated peptides and APCs from peri pheral blood of MG patients and healthy controls. With this assay we d etected the binding of the two peptides to the surface of intact APCs of both MG patients and control donors. Moreover, the presentation of peptide p259-271 by individuals with MG was significantly higher than that observed in healthy subjects. The peptides were specifically boun d to HLA class II determinants on the APCs, as shown by inhibition wit h antibodies to the HLA class II haplotypes of the individuals investi gated. Moreover, the binding of these peptides was in correlation with their ability to induce specific proliferative responses of periphera l blood T cells of these patients. The ability to screen for potential ly pathogenic epitopes in each patient is of importance for the future design of specific inhibitory analogues that might be used to treat M G.