THE MURINE (H-2(K)) T-CELL EPITOPES OF BEE VENOM PHOSPHOLIPASE A(2) 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 Aa from bee venom (PLA(2)) is a potent inducer of IgE antibody formation in CBA/J (H-2(k)) mice. In contrast, a recombinant mutant protein lacking enzymatic activity due to an amino acid exchange in the active site of the enzyme fails t o induce IEE antibodies under identical immunization conditions. Pepti de mapping and T-cell stimulation experiments with 18-mer overlapping peptides locate the T-helper cell-activating epitopes in the C-termina l region of the PLA(2) protein. No T-cell epitopes are found in the ar ea around position 34, the center of the enzymatically active site. Th e data support a model in which initially an enzymatic activation of m ast cells or basophiles leads to IL-4 production which in a paracrine way drives T-helper cells, concomitantly activated by antigen, into Th 2 differentiation. This ultimately favors B-cell activation for an IgE response.