Generation of acetylcholine receptor-specific human T cell lines using heterobifunctional antibody-targeted antigen presentation.

Characterizing AChR-specific T lymphocyte clones is an important step towards the ability to induce antigen-specific tolerance in myasthenia gravis (MG). However, the limited supply of relatively inefficient autologous antigen presenting cells (APCs) makes establishing AChR-specific T lymphocyte lines difficult. In this study we targeted AChR to autologous surface IgM+ (sIgM+) APCs using heterobifunctional antibodies (bi-Ab) consisting of anti-sIgM linked to anti-AChR antibodies. FACScan analysis and whole cell-based radioimmunoassay (RIA) showed binding of bi-Ab/AChR conjugates to sIgM+ APCs. Using antigen targeting, AChR-presentation to a well-characterized AChR-specific T cell clone, and to T cell lines raised de novo from MG thymocytes, was improved. Thus, antigen targeting using bi-Ab improved the efficiency of presentation of the scarce autoantigen AChR, suggesting that this method might allow the use of relatively impure antigen preparations and normally inefficient non-antigen-specific APCs, including those which can be immortalized, to accelerate the characterization of the AChR epitopes recognized by pathogenic T helper lymphocytes.