Synthetic immunogens constructed from T-cell and B-cell stimulating peptides (T:B chimeras): preferential stimulation of unique T- and B-cell specificities is influenced by immunogen configuration.
In our effort to develop synthetic immunogens as vaccines, we have focused on the combination of a known T-cell stimulating peptide with putative B-cell stimulating peptide epitopes derived from the sequences of respiratory syncytial (RS) virus proteins. The T-cell stimulating peptide consists of residues 45 through 60 of the 1A protein of RS virus, and it also contains an overlapping antibody binding (B-cell) site. Herein, we have combined the 1A T-cell stimulating peptide with a putative B-cell peptide epitope derived from the viral G glycoprotein using linear synthesis or using chemical crosslinking. The chimeric immunogens were compared to each other and to free peptides for their T- and B-cell stimulating properties. Both chimeras had potent T-cell stimulating and antibody-inducing activity. However, T-cells primed to free peptide differentially recognized the two chimeras and immunization with the chimeras primed T-cells with different specificity. Most strikingly, the two chimeras had opposite antibody-inducing properties: The chimera constructed by linear synthesis overwhelmingly elicited antibody directed against the G peptide, whereas the chimera constructed by chemical crosslinking overwhelmingly elicited antibody directed against the 1A peptide. Competition blocking studies revealed that the chimeras adopted different configurations in solution. The resulting antibody response, and hence the B-cell clone elicited, was consistent with the antibody accessibility of the individual peptide epitope.
Department of Infectious Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
M E
ME
Levely
M A
MA
Mitchell
J A
JA
Nicholas
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001667:Binding, Competitive; D000939:Epitopes; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D010455:Peptides