Comparison of primary sensitization of naive human T cells to varicella-zoster virus peptides by dendritic cells in vitro with responses elicited in vivo by varicella vaccination

Dendritic cells (DC) are potent APC during primary and secondary immune res ponses. The first objective of this study was to determine whether human DC mediate in vitro sensitization of naive CD4(+) T cells to epitopes of the immediate early 62 (IE62) protein of varicella tester virus (VZV), The indu ction of CD4(+) T cell proliferative responses to eight synthetic peptides representing amino acid sequences of the VZV IE62 protein was assessed usin g T cells and DC from VZV-susceptible donors. The second objective was to c ompare in vitro responses of naive T cells with responses to VZV peptides i nduced in vivo after immunization with varicella vaccine. T cell proliferat ion was induced by three peptides, P1, P4, and P7, in 71-100% of the donors tested before and after vaccination using DC as APC, Monocytes were effect ive APC for VZV peptides only after immunization. Two peptides, P2 and P8, induced naive T cell proliferation less effectively and were also less immu nogenic for T cells from vaccinated or naturally immune donors, T cell reco gnition of specific peptides was concordant between naive, DC-mediated resp onses, and postvaccine responses using monocytes as APC in 69% of compariso ns (p = 0.05; chi(2)); the predictive value of a positive response to an IE 62 peptide before immunization for T cell sensitization in vivo was 82%, Th ese observations indicate that primary T cell responses detected in vitro u sing DC as APC may be useful to characterize the potential immunogenicity o f viral protein epitopes in vivo.