TH1 but not TH0 cell help is efficient to induce cytotoxic T lymphocytes by immunization with short synthetic peptides

Abstract

Immunization of BALB/c mice with peptide HVSGHRMAWDMMMNWA, encompassing residues 121-135 from hepatitis C virus E1 protein, induced CD4 ⍣ T h 1 cells as well as a long-lasting CD8 ⍣ cytotoxic T lymphocyte (CTL) response in vivo when the peptide was administered s.c. with or without incomplete Freund's adjuvant. Using truncated peptides from this sequence it was shown that the determinant recognized by cytotoxic T cells was encompassed by residues SGHRMAWDM. Deletion of residues from the N-terminus or the C-terminus of the wild-type peptide abrogated its helper character. When Val122 of the wild peptide was replaced by Ala, the ability to induce a cytotoxic response was lost concomitantly with the loss of the T h 1 pattern of cytokine production. Interestingly, the Ala-modified peptide, when co-immunized with a peptide encompassing residues 323-329 from ovalbumin (OVA), which is able to induce a T h 1 response in BALB/c mice, restored the capacity of the modified peptide to induce CTL. However, co-immunization of the Ala-modified peptide with a peptide encompassing residues 106-118 from sperm whale myoglobin, which induces a T h 0 cytokine profile in BALB/c mice, was much less efficient than the OVA peptide to restore CTL induction. These results demonstrate that CTL induction with a short synthetic peptide requires that this peptide contains domains recognized by T c cells as well as by T h 1 cells. For those peptides that do not contain this type of T h domain, competent T cell help can be provided by co-immunization with a distinct peptide that is able to stimulate a T h 1 response.

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

“…CD4 ϩ Th cells play an important role on the induction of CTL (23,(31)(32)(33)(34). However, it has also been described that depletion of CD4 ϩ T cells may favor the induction of CTL responses (14,22,35), and enhance the therapeutic efficacy in tumor rejection (14,35) suggesting that CD4 ϩ T cells play a regulatory role.…”

“…Many studies, including our own, have described the role of CD4 ϩ T cells in providing help for the induction of CTLs (23,(31)(32)(33)(34)36). However, CD4 ϩ T cells can coordinate other antitumor effector pathways independent of CTLs (37).…”

Induction of Hepatitis C Virus E1 Envelope Protein-Specific Immune Response Can Be Enhanced by Mutation of N-Glycosylation Sites

“…Spleens of mice were removed 2 weeks after the final injection. Splenocytes were incubated in the presence of two different peptides: H16A, which has been shown to contain a CD8 ϩ and a CD4 ϩ epitope in the context of a genotype 1b sequence, and G10A, which corresponds to the CD8 ϩ epitope present in the H16A peptide (30). The H16A peptide used here derives from a subtype 1a E1 sequence and contains two mutations located in the CD4 ϩ determinant compared with the 1b peptide originally described in the literature (Fig.…”

Identification and Characterization of a T-Helper Peptide from Carcinoembryonic Antigen

“…The pattern of cytokines liberated by the HTLs, as well as direct cell-to-cell contact through molecules such as CD40-CD40L, determine the fate of the response. Immunization experiments with peptide constructs (or peptide mixtures) containing THds and B-cell epitopes (21,22) or TCds (23)(24)(25) have been very useful not only to understand the role of THds in antibody and CTL induction but to provide general guidelines for the use of synthetic peptides as components of a vaccine. Thus, characterization of THd in the sequence of tumor antigens is of paramount importance for the development of antitumor vaccines as well as the monitoring of T-cell responses in cancer patients.…”