Noncovalent association with stress protein facilitates cross-priming of CD8+ T cells to tumor cell antigens by dendritic cells.

摘要: A viral oncogene carrying well-defined K(b)/D(b)-restricted epitopes was expressed in a heat shock protein (hsp)-associated or nonassociated form the murine tumor cells P815 and Meth-A. Wild-type SV40 large T-Ag (wtT-Ag) is without stable hsp association; mutant (cytoplasmic cT-Ag) chimeric (cT272-green fluorescent fusion protein) association with constitutively expressed, cytosolic hsp73 (hsc70) protein. In vitro, remnants from apoptotic wtT-Ag- cT-Ag-expressing are taken up processed by immature dendritic (DC), K(b)/D(b)-binding T1, T2/3, T4 of cross-presented to CTL TAP-independent way. DC pulsed transfected, three more efficiently when they ATP-sensitive hsp73/cT-Ag complexes than hsp-nonassociated (native) T-Ag. vivo, IFN-gamma-producing CD8+ T were elicited DNA vaccine that encoded hsp73-binding native, non-hsp-binding Three- 5-fold higher numbers (T1-, T2/3-, T4-) specific, D(b)/K(b)-restricted primed during growth transfected H-2(d) Meth-A/cT tumors Meth-A/T F(1)(b x d) hosts. Hence, an facilitates cross-priming vitro vivo process material cells.