Cholera toxin increases intracellular pH in B lymphoma cells and decreases their antigen-presenting ability.
Cholera toxin (CT) can function as a potent adjuvant in the mucosal immune response. However, we have found that treatment of A20-HL murine B lymphoma cells with CT severely inhibits the presentation of ovalbumin (OVA) to cells of the T cell clone 42-6A specific for OVA(323-339)/I-Ad, whereas it does not affect the presentation of OVA(323-339) peptide. CT treatment did not affect the expression of B7-1, B7-2, ICAM-1, LFA-1 or MHC class II on, or the internalization of OVA into A20-HL cells. In CT-treated A20-HL cells, degradation of OVA was decreased, and intracellular pH was raised to a level approximately equivalent to that in CH3NH2-treated cells. Treatment with CH3NH2 is known to raise the pH in endocytic structures and thus inhibits antigen processing. Treatment of A20-HL cells with dibutyryl-cAMP similarly increased intracellular pH. The increase in intracellular pH following CT treatment was inhibited by a cAMP inhibitor, 2',3'-dideoxyadenosine. These results strongly suggest that CT treatment of A20-HL cells inhibits their antigen-presenting cell function by triggering the cAMP cascade, increasing intracellular pH, and reducing the degradation of OVA.
Tanaka
Y
Y
Department of Immunology, Toho University School of Medicine, Tokyo, Japan.
Nakano
H
H
Ishikawa
F
F
Yoshida
M
M
Gyotoku
Y
Y
Kakiuchi
T
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002645:Chickens; D002772:Cholera Toxin / Q000276:immunology* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid; D016393:Lymphoma, B-Cell; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D014407:Tumor Cells, Cultured
D010047:Ovalbumin; D002772:Cholera Toxin