Lupus autoantigens: their origins, forms, and presentation.
The immune system has developed a number of mechanisms by which to distinguish self from foreign proteins. These mechanisms are found throughout the ontogeny of B and T cell development and include the deletion of autoreactive cells in central lymphoid organs and the induction of self-tolerance in the periphery. However, any failure of these mechanisms for self-tolerance may result in autoimmune disease. Efforts in our laboratory have been directed at understanding how autoimmunity is initiated and maintained in both the 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 "antigenic sin" of SLE and in the role of B lymphocytes as autoantigen presenting cells. We will also discuss whether costimulation is a formal requirement for the induction and maintenance of autoimmunity. Finally, we have provided a model for how all of these individual elements may contribute to the autoimmune processes leading to pathology.
Doyle
H A
HA
Yale University School of Medicine, New Haven, CT 06520-8031, USA.
Yan
J
J
Liang
B
B
Mamula
M J
MJ
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD; D001224:Aspartic Acid / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice
D015703:Antigens, CD; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D001224:Aspartic Acid