T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns

Background: Secreted phospholipases A(2) (sPLA(2)) represent antigens to which humans may be rarely or frequently exposed. Thus, the investigation of humoral and cellular immune responses to sPLA(2)s from different species can provide a suitable model in the study of antibody and T-cell cross-reactivity. Methods: Specific IgE, IgG(1), IgG(4), and IgA antibodies were analyzed by ELISA against sPLA(2)s from pancreas of Bos taurus (BT), Apis mellifera (AM) bee venom, Daboia russellii (DR) and Naja mossambica (NM) snake venoms, and human group III (hGIII) sPLA(2) using sera of nonallergic beekeepers, AM-allergic patients, and healthy controls. T-cell cross-reactivity was investigated in PBMC, and T-cell clones (TCC) are generated against AM sPLA(2). Results: Hyperimmune and allergic individuals showed high levels of sPLA(2)-specific IgG(4) and significant IgG(4) cross-reactivity between BT, DR, and NM sPLA(2)s. Furthermore, IgE, IgA, and IgG(1) cross-reactivities against BT, DR, and NM sPLA(2)s were also detectable in the range of 22.2-44.8%. Allergic patients showed significant T-cell proliferative response to NM sPLA(2) together with increased IFN-gamma and IL-13 production even though they had never been exposed to cobra venom. Although nonallergic healthy controls show no cross-reactivity at T-cell level, they did have low levels of IgG(4) and IgA against BT, DR, and NM sPLA(2)s. Human TCC spanning three major T-cell epitopes of AM sPLA(2) showed minor proliferative response to NM and hGIII sPLA(2)s. Conclusions: This study shows that T cells and antibodies may show cross-reactivity between different species without being naturally exposed to sPLA(2)s.