Lupus autoantigens: Their origins, forms, and presentation

The immune system has developed a number of mechanisms by which to distingu ish self from foreign proteins. These mechanisms are found throughout the o ntogeny of B and T cell development and include the deletion of autoreactiv e cells in central lymphoid organs and the induction of self-tolerance in t he periphery. However, any failure of these mechanisms for self-tolerance m ay result in autoimmune disease. Efforts in our laboratory have been direct ed at understanding how autoimmunity is initiated and maintained in both th e B and T cell compartment, with particular interest in the autoimmunity of systemic lupus erythematosus (SLE). This review will focus on our studies on the forms of self-antigens that may be involved in the original "antigen ic sin" of SLE and in the role of B lymphocytes as autoantigen presenting c ells. We will also discuss whether costimulation is a formal requirement fo r the induction and maintenance of autoimmunity. Finally, we have provided a model for how all of these individual elements may contribute to the auto immune processes leading to pathology.