The murine (H-2k) T-cell epitopes of bee venom phospholipase A2 Lie outside the active site of the enzyme. Implications with respect to a paracrine activation of Th2 cells for an IgE antibody response.
Recombinant, enzymatic active phospholipase A2 from bee venom (PLA2) is a potent inducer of IgE antibody formation in CBA/J (H-2k) mice. In contrast, a recombinant mutant protein lacking enzymatic activity due to an amino acid exchange in the active site of the enzyme fails to induce IgE antibodies under identical immunization conditions. Peptide mapping and T-cell stimulation experiments with 18-mer overlapping peptides locate the T-helper cell-activating epitopes in the C-terminal region of the PLA2 protein. No T-cell epitopes are found in the area around position 34, the center of the enzymatically active site. The data support a model in which initially an enzymatic activation of mast cells or basophiles leads to IL-4 production which in a paracrine way drives T-helper cells, concomitantly activated by antigen, into Th2 differentiation. This ultimately favors B-cell activation for an IgE response.
Specht
C
C
Institute for Immunology, University of Münster, Germany.
Kölsch
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001514:Bee Venoms / Q000201:enzymology*; D001665:Binding Sites / Q000276:immunology; D000939:Epitopes; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010741:Phospholipases A / Q000276:immunology*; D054467:Phospholipases A2; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D001514:Bee Venoms; D000939:Epitopes; D010455:Peptides; D007073:Immunoglobulin E; D010741:Phospholipases A; D054467:Phospholipases A2