INDUCTION OF A CD8(-LYMPHOCYTE RESPONSE BY CROSS-PRIMING REQUIRES COGNATE CD4(+) T-CELL HELP() CYTOTOXIC T)

Class I-restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can ga in entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I-restrict ed cytotoxic T lymphocyte (CTL) cross-priming directed against a varie ty of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate respo nses to selected self components. In both cases, this presentation app ears to require the active involvement of a bone marrow-derived antige n presenting cell (APC). Here, we show that CTL induction by cross-pri ming with cell-associated ovalbumin requires the active involvement of CD4(+) helper T cells. Importantly, this CD4(+) population is only ef fective when both the helper and CTL determinants are recognised on th e same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4(+) T cell actively modifies the APC, conv erting it into an effective stimulator for the successful priming of t he CTL precursor.