Direct evidence for functional self-protein/Ia-molecule complexes in vivo.
Through the development of a panel of murine hybridomas reactive to murine hemoglobin, we have been able to study the processing and presentation of self antigens by antigen-presenting cells. Our results demonstrate that peritoneal macrophages in vivo can process and potentially present the self-antigen hemoglobin. We have extended this finding to show that, directly after removal from the mouse, antigen-presenting cells from a variety of tissues stimulate our hemoglobin-specific hybridomas without any manipulation or addition of exogenous antigen. This constitutes direct functional proof that in a nondisease state self proteins are processed constitutively and can be presented in a fashion similar to that in which foreign antigens are presented. Our demonstration that antigen-presenting cells can process and potentially present self as well as foreign molecules implies that self-tolerance occurs at the level of the T cell. This constitutive processing and presentation of self antigens has potentially far-reaching implications in self-tolerance, autoimmunity, and alloreactivity.
Lorenz
R G
RG
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
Allen
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D005914:Globins / Q000276:immunology; D006454:Hemoglobins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; D005914:Globins