Antigen processing: approaches for dissecting subcellular mechanisms that form the basis for T-cell responses modulating allergic reactions.
Antigen processing determines the production of peptides from antigens, including allergens, and their binding to class II major histocompatibility complex (MHC-II) molecules, which stimulate T-cell responses. Our studies have addressed the cell biology and biochemistry of the MHC-II antigen processing pathway using subcellular fractionation of macrophages on Percoll density gradients, coupled with other techniques. We have isolated a high density, late endocytic antigen processing compartment, with lysosomal properties, that contains a high level of MHC-II molecules, as assessed by several techniques. Moreover, the direct formation of peptide MHC-II complexes was demonstrated within this compartment, using a T hybridoma assay for peptide MHC-II complexes present in subcellular fractions of macrophages previously exposed to the model antigen, hen's egg-white lysozyme. These observations support an important role for this compartment in the class II major histocompatibility complex antigen processing pathway.
Harding
C V
CV
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44120, USA.
D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex; D002478:Cells, Cultured; D004705:Endocytosis / Q000276:immunology; D011992:Endosomes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology; D051379:Mice; D008808:Mice, Inbred CBA; D009113:Muramidase / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology
D000936:Antigen-Antibody Complex; D000949:Histocompatibility Antigens Class II; D009113:Muramidase