Concomitant Helper Response Rescues Otherwise Low Avidity CD8+ Memory CTLs to Become Efficient Effectors In Vivo

This report seeks a means of maximizing memory CD8 T cell responses to peptide immunization. Delivery of the CD8 peptide epitope by stress protein, heat shock protein (hsp)70, results in excellent immunogenicity at the acute phase but memory responses were poor both in terms of the number of responding cells as well as their functional avidity. We demonstrate for the first time that hsp70 can also be used as a vehicle to achieve CD4 T cell responses to loaded peptide epitopes and that coimmunization with hsp70 loaded with both CD8 and CD4 peptide epitopes may increase memory up to 3-fold. Furthermore, CD8+ T cell memory responses were of higher avidity measured both by in vitro cytotoxicity assays and a new methodology that measures the avidity of CTL activity in vivo in mice. Our results emphasize that peptide immunization remains a viable approach to induce long-term CD8+ T cell function, providing steps are taken to assure appropriate stimulation of Th cell responses.