EVIDENCE OF IDIOTYPIC MODULATION IN THE IMMUNE-RESPONSE TO GP43, THE MAJOR ANTIGENIC COMPONENT OF PARACOCCIDIOIDES-BRASILIENSIS IN BOTH MICE AND HUMANS

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin Am erica, with a high prevalence in Brazil, Argentina, Colombia and Venez uela. The aetiologic agent of disease is a thermal dimorphic fungus, P aracoccidioides brasiliensis. A glycoprotein of 43 000D (gp43) is the major antigen of P. brasiliensis. Antibodies directed to this antigen are detected in the sera of all patients with PCM. Gp43 binds to lamin in, thus participating in adhesion, invasion and pathogenesis of the f ungus. As the role of antibodies in PCM is not fully understood, we de cided to investigate the outcome of mice immunization with three disti nct anti-gp43 MoAbs (17c, 8a and 24a) coupled with keyhole limpet haem ocyanin (KLH). Results show not only the expected presence of anti Id (AB2) antibodies in the sera of these animals but also a spontaneous a nd increasing amount of anti-anti-Id (AB3) antibodies after the third course of immunization. Hybridomas producing both AB2 and AB3 MoAbs we re obtained using spleen cells from mice immunized with MoAb 17c. AB3 MoAbs were also obtained with spleen cells of mice immunized with MoAb s 8a and 24a. It was also shown that human PCM patients' sera with hig h titres of anti-gp43 antibodies generate anti-Id antibodies. These da ta suggest that the immune response to P. brasiliensis can be spontane ously modulated by the idiotypic network.