Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation

Abstract A major drawback of subunit vaccines is their inability to generate cytolytic T lymphocytes (CTL), a deficit attributed to segregation of the class I and class II antigen-processing pathways. We sought to understand processes involved in CTL induction by three proprietary adjuvants: Tomatine, PROVAX™, and a synthesized glycolipid (Glc-N-(8/16), Glycolipid). We used in vivo models to investigate antigen uptake, macrophage involvement, TAP-independent processing, and costimulatory molecule dependencies. Glycolipid required splenic and lymph node macrophages, whereas Tomatine generated CTL independently of either macrophage population. In contrast, PROVAX™ showed partial macrophage requirements. Immunized TAP knockout mice revealed that ovalbumin (OVA)–Tomatine and OVA–PROVAX™, but not OVA–Glycolipid, generate class I–peptide complexes. All three immunostimulants also elicited CD86-dependent T H 1 cytokine responses.