Cholera toxin increases intracellular pH in B lymphoma cells and decreasestheir 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 cel ls of the T cell clone 42-6A specific for OVA(323-339)/I-A(d), whereas it d oes not affect the presentation of OVA(323-339) peptide. CT treatment did n ot affect the expression of B7-1, B7-2, ICAM-1, LFA-I or MHC class II on, o r 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 lev el 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 a ntigen-presenting cell function by triggering the cAMP cascade, increasing intracellular pH, and reducing the degradation of OVA.