A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins

A 65 kDa mycobacterial heat shock protein (hsp65), fused to a polypeptide t hat contains an octapeptide (SIYRYYGL) agonist for a particular T cell rece ptor (2C TCR), stimulated C57BL/6 mice as well as CD4-deficient mice to pro duce CD8(+) cytolytic T lymphocytes (CTL) to the fusion partner's octapepti de. This and other hsp65 fusion proteins but not native hsp65 itself stimul ated dendritic cells in vitro and in vivo to upregulate the levels of MHC ( class I and II) and costimulatory (B7.2) molecules. The results suggest a m echanism for the general finding that hsp fusion proteins, having fusion pa rtners of widely differing lengths and sequences, elicit CD8 CTL to peptide s from the fusion partners without requiring exogenous adjuvents or the par ticipation of CD4(+) T cells.