Fusion proteins with heterologous T helper epitopes. Recombinant E. coli heat-stable enterotoxin proteins.
Fusion proteins containing specific B cell and T cell epitopes were used to examine how the intramolecular arrangement of T and B cell epitopes within a chimeric protein influences antigen-specific B cell antibody responses as well as specific T cell activation. Chimeric proteins, containing single or multiple copies of the Th epitope ovalbumin 323-339 (ova) linked at different positions to STa, the heat-stable enterotoxin of E. coli, were compared with respect to their ability to induce STa-specific antibody production and to induce ova-specific T cell activation. Chimeric proteins induced ova-dependent antibody production against STa at the amino terminal end, irrespective of the positioning of ova. Multiple tandem copies of ova in any position led to increased levels of antibody production against this epitope. In contrast, T cell help for antibody production against a second B cell epitope at the carboxy terminus of the fusion proteins was more effective after insertion of multiple copies of ova in a distal than in an adjacent position. A fusion protein, containing four copies of ova effectively elicited T cell help for antibody production against both examined B cell determinants, showing that activated Th cells recognizing a single epitope could simultaneously provide help for distinct sets of B cells specific for widely separated epitopes within a protein. T cell recognition of ova in all chimeric peptides, independently of its position, following the same pattern of genetic restriction (i.e. immunodominant in H-2d and nonimmunogenic in H-2k) as in the native ovalbumin molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
Löwenadler
B
B
Kabi Pharmacia BioScience Center, Stockholm, Sweden.
Lycke
N
N
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D029968:Escherichia coli Proteins; D006801:Humans; D006825:Hybridomas; D010047:Ovalbumin / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; C034151:heat stable toxin (E coli); D010047:Ovalbumin