Fine specificity of cytotoxic T lymphocytes primed in vivo either with virus or synthetic lipopeptide vaccine or primed in vitro with peptide

Standard synthetic peptide preparations contain numerous peptidic byproducts in small amounts, which may be efficiently recognized by cytotoxic T lymphocytes (CTL). Recognition patterns of such peptide mixtures by CTL may serve as a kind of fingerprint for CTL fine specificity. Three types of H-2Db-restricted CTL were compared in this way. CTL primed in vivo either with A/PR/8/34 influenza virus or with a synthetic lipopeptide vaccine prepared from influenza nucleoprotein (NP) peptide 365-380 showed identical fine specificity. Both recognize virus-infected cells. In contrast, CTL primed in vitro with NP 365-380 had a different fine specificity and they did not recognize virus-infected cells. Most significantly, the two in vivo primed CTL types efficiently recognized the natural viral nonapeptide NP 366-374 presented by virus-infected H-2b cells, whereas the in vitro primed CTL failed to do so.