Reveromycin A inhibits antigen receptor-mediated antigen presentation by B lymphoma cells via its effect on intracellular trafficking

Reveromycin A (Rev.A) is an inhibitor of epidermal growth factor-dependent cell growth that is produced from the culture broth of an actinomycete strain. Rev.A was assessed for its ability to regulate antigen (Ag) presentation by A20-HL B lymphoma cells bearing trinitrophenyl (TNP)-specific surface IgM (sIgM) to cloned T cells specific for OVA(323similar to339)/I-A(d). Rev.A-treatment inhibited the presentation of Ag internalized via sIgM, but not of Ag via fluid-phase pinocytosis. Rev.A-treatment decreased protein synthesis, but a similar decrease in protein synthesis by cycloheximide induced much less inhibition of sIgM-mediated Ag presentation. Rev.A-treatment decreased the rate of re-expression of sIgM in A20-HL cells, the amount of Ag internalized via sIgM during 3 hours of incubation, and the generation of antigenic peptides from TNP-OVA internalized via sIgM. Rev.A-treatment was suggested to affect intracellular trafficking from early endosomes into late endocytic compartments of Ag internalized via sIgM. Rev.A might provide a useful tool for studying intracellular transport of Ag, especially Ag internalized via sIgM.