Myasthenia gravis and its animal model: T cell receptor expression in an antibody mediated autoimmune disease.
Myasthenia gravis (MG) is a prototypic antibody-mediated autoimmune disease. Since the primary target antigen of the autoimmune response is known and a well-characterized animal model is available, MG is often considered an excellent situation for the application of novel specific immunotherapies, many of which are directed at T lymphocytes. CD4+ helper T cells are required for the development of the animal model, experimental autoimmune MG (EAMG). Even though the target antigen, acetylcholine receptor (AChR) is immunologically complex, the T cell response to AChR in mice is dominated by recognition of a single peptide by about 50% of the T cells. These T cells, in turn, utilize a restricted set of TCR gene elements and conserved CDR3 regions. While specific therapy directed at the immunodominant T cells is capable of reducing the magnitude of the anti-AChR response, considerable flexibility is apparent and reveals the ability of additional T cells to provide the requisite B cell help. In human MG patients, AChR-specific T cells have been identified but in many studies the frequencies were surprisingly low. In a very few cases, AChR-specific T cells have been cloned from MG patients. Analysis reveals heterogeneity in epitope recognition and MHC restriction. Little information on TCR structure is available. Our own studies using antigen-specific as well as non-specific methods for examining clonal T cell expansions in MG have led to an alternative hypothesis concerning T-B collaboration in MG.
Infante
A J
AJ
Department of Pediatrics, University of Texas Health Science Center at San Antonio, 78284-7810, USA.
Kraig
E
E
D000818:Animals; D017951:Antigen Presentation; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D001323:Autoantibodies; D011948:Receptors, Antigen, T-Cell