Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.

Abstract

Antiviral cytotoxic T lymphocytes (CTL) are specifically induced against viral antigens presented by MHC class I molecules on the surface of infected cells (1). The intracellularly synthesized antigens are processed and associated with class I antigens within cells in a yet poorly defined way before presentation on the cell surface (2). Induced effector CTL also recognize synthetic peptides bound by MHC class I molecules from without on the cell surface in absence of an apparent need for cell internal processing (3, 4).Virus-specific CTL have been shown to be crucially involved in recovery from and in protection against lymphocytic choriomeningitis virus (LCMV) (5) and many other virus infections . Induction ofCTL response is best achieved in vivo by priming with replicating virus. Since vaccination with live virus may cause, although rarely, some disease, means have been sought for many years to induce virus-specific CTL responses in vivo with nonreplicating synthetic virus antigens .In the past few years in vivo priming of class I-restricted T cells with free proteins or peptides was shown for ovalbumin with whole soluble protein (6) or tryptic digests of the whole protein or relatively large peptides of the relevant T cell epitope ofovalbumin (7,8). Recently it was shown that short synthetic peptides of influenza virus nucleoprotein can induce specific responses in vivo to the priming peptide as well as to the virus; induction was possible with chemically modified peptides linked to a lipid component but not with free peptides (9).We evaluated whether the free unmodified 15-mer peptide (RPQASGVYMGN-LTAQ) representing a H-2a T cell epitope of LCMV nucleoprotein (10, 11) could induce in vivo a specific CTL response to LCMV and we report on the successful demonstration ofsuch a response. Although stringently restricted to the class I MHC allele for the peptide used, these results demonstrate the feasibility ofusing unmodified T cell epitope peptides as antiviral vaccines in principal .

Partial Activation of Neonatal CD11c+ Dendritic Cells and Induction of Adult-Like CD8+ Cytotoxic T Cell Responses by Synthetic Microspheres

“…1). It should be noted that CTL responses to LCMV 118 -132 are not induced by immunization with free synthetic peptide alone (32,33), such that these CTL responses are directly attributable to the use of MS as Ag delivery system. Considering the lower proportion of CD8 ϩ T cells in the spleen of neonates (which persists after in vitro restimulation, not shown), this indicated a significant cytotoxic potential of neonatal CTLs.…”

Induction of CTL and Nonpolarized Th Cell Responses by CD8α+ and CD8α− Dendritic Cells

“…Both DC subpopulations were loaded with various concentrations of three different peptides (Table I): peptide p 103-116 corresponding to the sequence 103-116 of the VP1 protein from poliovirus type 1, which contains an immunodominant CD4 ϩ T cell determinant I-E d restricted (22), peptide p 118 -126 corresponding to the H-2 d class I-and class II-restricted T cell epitope from the nucleoprotein of the LCMV (19,20), and peptide p 257-264 corresponding to the H-2 b class I-restricted T cell epitope encompassing the OVA residue 257-264 (21). All these peptides were endotoxin free, as mentioned in Materials and Methods, and did not induce DC maturation, at least after 90 min of incubation (Table II).…”

“…The synthetic peptide RPQASGVYM carrying the 118 -126 sequence from the lymphocytic choriomeningitis virus (LCMV) nucleoprotein corresponding to a class I and class II H-2 d -restricted CTL epitope (19,20), the synthetic peptide SIINFEKL carrying the 257-264 sequence from OVA corresponding to a H-2K b -restricted CTL epitope (21), and the synthetic peptide KLFAVWKITYKDTV carrying the 103-116 sequence from the poliovirus I envelope protein VP1 corresponding to a I-E d -restricted Th epitope (22) were purchased from Neosystem (Strasbourg, France). All peptides and their restriction elements are described in Table I.…”

Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

“…Animal studies have shown that antigenic peptides can be used to induce a CTL response when administered with certain adjuvants ( 17), and in liposomes ( 18), or by direct attachment of lipids (10)(11)(12). However, we are not aware of studies that have been carried out in humans using antigenic peptides to specifically elicit a primary CTL response.…”