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

Abstract

SummaryThe 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 MSA2 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 D I 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.

Self‐Organization of a Chiral D‐EAK16 Designer Peptide into a 3D Nanofiber Scaffold

“…There is some discussion about using D ‐peptides for chaperone systems39 and for inducing protective immunity 40. Shai and colleagues reported that a synthetic D ‐amino acid peptide that corresponded to the N‐ terminal sequence of HIV‐1 gp41 ( D ‐WT) of HIV‐1 associates with its enantiomeric wild‐type fusion (WT) peptide in the membrane and inhibits cell fusion mediated by the HIV‐1 envelope glycoprotein 41.…”

Nonhuman Primates

“…Differences in degree of susceptibility or immunity to experimental malarial infection and differences in serum proteins correspond to the red-or gray-necked group type. While the owl monkey is an excellent animal model for human malaria and its treatment, it has also been identified as a model for studies of oncogenic viruses, particularly herpesviruses (Barhona et al, 1976;Vernot et al, 2005), and nononcogenic viruses such as hepatitis A (Asher et al, 1995;Balayan, 1992), and it has shown potential as a model for Eastern equine encephalitis virus (Espinosa et al, 2009) and dengue virus (Schiavetta et al, 2003). Both of these Aotus spp.…”

Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip fromHerpesvirus saimiri

“…HVS infection transforms both non-human primates and human T-cells to TCR-independent proliferation [ 18 – 20 ]. Tip binding to Lck and subsequent Lck activation are partially responsible for this effect [ 24 , 32 ].…”

“…HVS infection has been used in vitro in human and non-human primates ( Aotus spp.) as a strategy for T-cell transformation [ 18 – 20 ]. This would suggest that transformation mechanisms in human and Aotus T-cells could have the same molecular basis.…”