Natural human IgE peptide‐specific CTL inhibit human IgE production and eliminate U266 in HLA‐A2 transgenic rodents

Abstract

Cytotoxic T‐lymphocytes elicited against a human IgE peptide nonamer restricted to HLA‐A2.1, pWV inhibit human IgE production and lyse human IgE‐secreting U266. A high throughput cell‐based ELISA is correlated with FACS determination of upregulated MHC I in RMA‐S‐A2Kb cell line. The efficiency of lysis of U266 is optimized with A2Kb transgene that also facilitates interaction of murine α3 domain with murine CD8. Activated CTL also inhibit IgE production by A2Kb‐U266 and prevent its progression in A2Kb mice, tolerized with A2Kb‐U266. Validity of human IgE peptide immunization in targeting IgE‐secreting plasma cells is extended to murine IgE peptide in non‐transgenic normal BALB/c mice. CTL responses elicited by nonameric PI‐1 peptide in CpG are intermittent in protecting a concomitant allergen‐specific KLH response without eliminating the potential of IgE production. Following each successive round of vaccination, IgE responses are fully recovered in vivo; moreover, even during effective in situ IgE suppression, competent, undiminished antigen‐specific IgE production can still be elicited in vitro, indicating the potential. Taken together, the observation suggests that a relevant human natural IgE peptide may be employed as a CTL‐based vaccine for pan‐IgE human therapy against IgE‐mediated diseases.