Factors affecting the efficiency of CD8(+) T cell cross-priming with exogenous antigens

Processing of exogenous protein Ags by APC leads predominantly to presentat ion of peptides on class II MHC and, thus, stimulation of CD4(+) T cell res ponses. However, "cross-priming" can also occur, whereby peptides derived f rom exogenous Ags become displayed on class I MHC molecules and stimulate C D8(+) T cell responses. We compared the efficiency of cross-priming with ex ogenous proteins to use of peptide Ags in human whole blood using a flow cy tometry assay to detect T cell intracellular cytokine production. CD8(+) T cell responses to whole CMV proteins were poorly detected (compared with pe ptide responses) in most CMV-seropositive donors. Such responses could be i ncreased by using higher doses of Ag than were required to achieve maximal CD4(+) T cell responses. A minority of donors displayed significantly more efficient CD8(+) T cell responses to whole protein, even at low Ag doses. T hese responses were MHC class I-restricted and dependent upon proteosomal p rocessing, indicating that they were indeed due to cross-priming. The abili ty to efficiently cross-prime was not a function of the number of dendritic cells in the donor's blood. Neither supplementation or freshly isolated de ndritic cells nor use of cultured, Ag-pulsed dendritic cells could signific antly boost CD8 responses to whole-protein Ags in poorly cross-priming dono rs. Interestingly, freshly isolated monocytes performed almost as well as d endritic cells in inducing CD8 responses via cross-priming. In conclusion, the efficiency of cross-priming appears to be poor in most donors and is de pendent upon properties of the individual's APC and/or T cell repertoire. I t remains unknown whether cross-priming ability translates into any clinica l advantage in ability to induce CD8(+) T cell responses to foreign Ags.