MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site

Pertussis toxin (PT), 1 a protein released by Bordetella pertussis organisms, is a major virulence factor in whooping cough (1). Awide variety of biological effects have been attributed to the toxin, which include lymphocytosis, histamine release, insulin secre-tion, stimulation of IgE production, and adjuvanticity (2-4). An mAb to PT pro-tects mice challenged intracerebrally (i.c.) with virulent B. pertussis (5). A toxoided PT was therefore selected to be one of the two main component of an acellular whooping cough vaccine, now in clinical trials (6). However, the toxin is thought to be responsible for the harmful side effects associated with the current vaccine. There is speculation that active toxin present in whole cell vaccine, and perhaps chemically toxoided PT in acellular vaccine, may cause rare but serious reactions including a state of hypotonia and hyporesponsiveness, convulsions, and encepha-lopathy (7, 8). The genes coding for the five subunits of PT have been cloned and sequenced (9, 10). It was proposed that it may be possible to develop a safe but nonreactogenic vaccine by genetic manipulation of the toxin gene. We have recently demonstrate