SELECTIVE-INHIBITION OF II-DEPENDENT ANTIGEN PRESENTATION BY HELICOBACTER-PYLORI TOXIN VACA

A major virulence factor in the stomach chronic infection by Helicobac ter pylori is a protein toxin (VacA), which alters cell membrane traff icking of late endasomal/prelysosomal compartments. Its role in the ch ronic infection established by H. pylori is unknown. To test the possi bility that VacA alters antigen processing taking place in prelysosoma l compartments, we have used the well-established model of antigen pro cessing and presentation consisting of tetanus toxoid-specific human ( CD4(+)) T cells stimulated by autologous antigen-pulsed Epstein-Barr-v irus-transformed B cells. We found that VacA interferes with proteolyt ic processing of tetanus toxin and toroid and specifically inhibits th e Ii-dependent pathway of antigen presentation mediated by newly synth esized major histocompatibility complex (MHC) class II, while leaving unaffected the presentation pathway dependent on recycling MHC class I I. The results presented here suggest that VacA may contribute to the persistence of H. pylori by interfering with protective immunity and t hat this toxin is a new useful tool in the study of the different path ways of antigen presentation.