Herpesvirus saimiri immortalization of Aotus T lymphocytes specific for an immunogenically modified peptide of Plasmodium falciparum merozoite surface antigen 2

The Plasmodium merozoite surface antigen 2 (MSA2) is one of several candidates for a protective vaccine against malaria. Previous studies have shown that antibodies directed against the MSA2 variable region are not protective and that constant regions are non-immunogenic. However, modified peptides derived from constant regions can be rendered immunogenic and partially protective in Aotus monkeys. In this study, we reveal the establishment, using in vitro Herpesvirus samiri (HVS) infection, of an Aotus monkey T-cell line (AnTMSA2) specific for a modified immunogenic and partially protective peptide derived from a constant and highly conserved region of MSA2 (SKYSNTFINNAYNMSIRRSM). AnTMSA2 is a CD4 T lymphocyte expressing high levels of MHC class II molecules, CD58 and CD2, which are important for proliferation and growth. AnTMSA2 proliferates specifically in response to the modified monomeric MS A2 peptide sequence. It is also capable of specific antigen recognition after glycine-cysteine-polymerized sequence processing and presentation by autologous APC. Interestingly, AnTMSA2 presents cross-reactivity with D-peptide analogues in which residues in positions 8 and 9 were changed for N_DI _D residues. Therefore, at least for this particular sequence, polymerized D-peptides could be used for immunizing animals without losing the immunogenic epitope. AnTMSA2 presents a cytokine profile corresponding to a Th0-like pattern, which suggests that as a result of HVS immortalization AnTMSA2 is in transit from a Th2 to a Th1 pattern. Taken together our results suggest that Th2 T-cell induction and/or T-cell cross-reactivity generation by the modified peptide could be responsible for the immunogenic conversion observed in Aotus monkeys and that D-peptide analogues with longer half-lives could provide an alternative for inducing protective immunity.