Microbial and T cell-derived stimuli regulate antigen presentation by dendritic cells in vivo.
B cells and dendritic cells (DC) internalize and degrade exogenous Ags and present them as peptides bound to MHC class II molecules for scrutiny by CD4(+) T cells. Here we use an Ab specific for a processed form of the model Ag, hen egg lysozyme (HEL), to demonstrate that this protein is not efficiently presented by lymph node DC following s.c. immunization. HEL presentation by the DC can be dramatically enhanced upon coinjection of a microbial adjuvant, which appears to act by enhancing peptide loading onto MHC class II. CD40 cross-linking or the presence of a high frequency of T cells specific for HEL can similarly improve presentation by DC in vivo. For any of these activating stimuli, CD8alpha(+) DC consistently display the highest proportion of HEL-loaded MHC class II molecules. These data indicate that exogenous Ags can be displayed to T cells in lymphoid tissues by a large cohort of resident DC whose presentation is regulated by innate and adaptive stimuli. Our data further reveal the existence of a feedback mechanism that augments Ag presentation during cognate APC-T cell interactions.
Manickasingham
S
S
Immunobiology Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Reis e Sousa
C
C
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000502:physiology; D016827:CD8 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D023201:CD40 Ligand; C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase