Requirements for histoplasmin presentation by accessory cells to a Histoplasma capsulatum-reactive T-cell line.
We examined the pathways involved in presentation of native histoplasmin by adherent splenocytes (as a source of accessory cells) to JC1, a Histoplasma capsulatum-reactive murine T-cell line that is CD4+. JC1 did not respond to accessory cells that had been fixed with paraformaldehyde and then exposed to histoplasmin but did proliferate to antigen-pulsed cells that were subsequently fixed. Accessory cells that were coincubated with histoplasmin and sodium azide or 2-deoxy-D-glucose failed to induce proliferation of JC1. Moreover, accessory cells exposed to the lysosomotropic agents, chloroquine and ammonium chloride, were unable to present antigen. Monensin also inhibited presentation of histoplasmin if added to accessory cells concomitant with antigen. In contrast, accessory cells that had been pulsed with antigen for 2 hr and then exposed to each inhibitor for 2 hr stimulated proliferation of JC1. The antigen-presenting capacity of accessory cells that had been pulsed with histoplasmin for 2 hr was diminished considerably by subsequent treatment with phospholipase A2. Additional studies demonstrated that cerulenin, which depresses posttranslational lipid modification of proteins, abolished presentation of histoplasmin. The reactivity of JC1 was sharply reduced by anti-L3T4 (CD4) or by anti-I-Ab monoclonal antibody. The results not only indicate that presentation of histoplasmin requires active metabolic events within accessory cells, they also delineate the pathways involved in handling this antigen.
Department of Medicine, University of Cincinnati College of Medicine, OH 45267.
J E
JE
Harris
G S
GS
Deepe
D000643:Ammonium Chloride; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology*; D001386:Azides / Q000494:pharmacology; D002460:Cell Line; D002569:Cerulenin / Q000494:pharmacology; D002738:Chloroquine; D003847:Deoxyglucose / Q000494:pharmacology; D005557:Formaldehyde; D006658:Histoplasma / Q000276:immunology*; D006659:Histoplasmin / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008985:Monensin / Q000494:pharmacology; D010741:Phospholipases A; D054467:Phospholipases A2; D011108:Polymers; D011480:Protease Inhibitors; D019810:Sodium Azide; D013601:T-Lymphocytes / Q000276:immunology*; D013696:Temperature
D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D001386:Azides; D007166:Immunosuppressive Agents; D011108:Polymers; D011480:Protease Inhibitors; D000643:Ammonium Chloride; D002569:Cerulenin; D005557:Formaldehyde; D002738:Chloroquine; D006659:Histoplasmin; D008985:Monensin; D019810:Sodium Azide; D003847:Deoxyglucose; D010741:Phospholipases A; D054467:Phospholipases A2; C003043:paraform