The T cell response to the glycoprotein D of the herpes simplex virus: the significance of antigen conformation.
Synthetic peptides corresponding to the first 23 amino acids of the glycoprotein D molecule of herpes simplex virus have been used to immunize mice and examine the role of antigen conformation in T cell responses. The structure of the peptides was determined by circular dichroism studies and was shown to be consistent with theoretical structure predictions. T cell clones were found that could respond to peptides that were nonhelical, and this response, which was directed to the C-terminal determinant (residues 8-23), could be modified by a constrained N-terminal sequence (residues 1-7) of the peptide. Namely, substitution of Ala for Pro at position 7 induced an alpha-helix and inhibited the response. Furthermore, a response to the N-terminal part of the molecule seemed to be directed to the alpha-helix and correlated positively with calculated degree of helicity. This response was also modified, in this case, by the C-terminal part of the molecule. These results suggest that local secondary structure of an antigen may regulate T cell responses and that structural changes in the peptide antigen downstream from the determinant modify recognition of that determinant. Furthermore, antigen processing by the macrophage and antigen presentation of T cells appears to conserve antigen structural integrity.
E
E
Heber-Katz
M
M
Hollosi
B
B
Dietzschold
F
F
Hudecz
G D
GD
Fasman
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D002472:Cell Transformation, Viral; D000939:Epitopes; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000032:analysis; D018139:Simplexvirus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C039447:glycoprotein D, Human herpesvirus 1