Modulation of T-cell reactivity to synthetic peptide analogues of foot-and-mouth disease virus in sheep by amino acid substitutions

J N Flynn, G D Harkiss, Danielle Gunn-Moore, R DiMarchi

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The ability of synthetic peptide analogues of foot-and-mouth disease virus VP1 capsid protein to induce T-cell proliferation in vitro following immunization of sheep with the uncoupled peptides was assessed. Elevated T-cell responses were obtained to a 21-residue peptide containing VP1 residues 141-158, and a 40-residue peptide containing residues 200-213 and 141-158 linked via a diproline-serine spacer. In contrast, no significant T-cell response was obtained with a 19-residue peptide containing residues 200-213 alone. In an attempt to engineer T-cell reactivity to this peptide, a sequence motif found in many peptides recognized by human or mouse T-cells was introduced by amino acid substitution. Substitution of a glycine or an aspartic acid for an alanine at position 207 in the 19-residue peptide resulted in the introduction of two such motifs running consecutively. Immunization of sheep with these peptides resulted in significant T-cell proliferative responses and elevated antibody responses. Analysis of further sequence variants showed that T-cell responsiveness was maintained with peptides containing single amino acid changes within these motifs, provided position 207 was glycine. The results thus suggest that increased T-cell reactivity, might be engineered via sequence manipulation of the 200-213 component of the 40-residue synthetic peptide. Such an additional T-cell epitope in the 40-residue peptide could potentially result in superior neutralizing antibody responses directed against the major epitope in residues 141-160 of VP1.
Original languageEnglish
Pages (from-to)255-66
Number of pages12
JournalVeterinary Immunology and Immunopathology
Volume31
Issue number3-4
Publication statusPublished - Mar 1992

Keywords / Materials (for Non-textual outputs)

  • Amino Acid Sequence
  • Amino Acids
  • Animals
  • Antibodies, Viral
  • Antibody Formation
  • Aphthovirus
  • Capsid
  • Epitopes
  • Foot-and-Mouth Disease
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Peptides
  • Sheep
  • Sheep Diseases
  • T-Lymphocytes
  • Viral Proteins

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