The T-lymphocyte proliferative response to synthetic peptide antigens of defined secondary structure.
Immunodominant sites in proteins recognized by T lymphocytes are segments consisting of at least 7-8 amino acids. It has previously been proposed that these sites in proteins are alpha-helical and amphipatic structures. We synthesized and investigated the immunogenicity of three synthetic peptides (MP7, MP8, and MP9), each consisting of the same 15 amino acids, but differing with respect to sequence. Based on information analysis and circular dichroism measurements, MP7 was shown to have an alpha-helical secondary structure and, based on previously assigned hydrophilicity indices, was also strongly longitudinally amphipatic. MP8 also was conformed as an alpha-helix, but was amphipatic in the sense that the N-terminal half of the molecule was hydrophilic and the C-terminal half hydrophobic. MP9 had neither an amphipatic nor alpha-helical structure. All three peptides were immunogenic in some strains of mice but none was immunogenic in all strains. This supports other studies concluding that amphipaticity per se is neither a necessary nor sufficient requirement for immunogenicity of a peptide. On the other hand, the present experimental data suggest that longitudinally amphipatic alpha-helical peptides may function better as T-cell determinants than the other peptides investigated.
Mouritsen
S
S
Institute for Experimental Immunology, University of Copenhagen, Denmark.
Meldal
M
M
Rubin
B
B
Holm
A
A
Werdelin
O
O
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000138:chemical synthesis / Q000276:immunology*; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000941:Antigens; D000939:Epitopes; D010455:Peptides