title: T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns.
abstract: BACKGROUND
  Secreted phospholipases A2 (sPLA2) represent antigens to which humans may be rarely or frequently exposed. Thus, the investigation of humoral and cellular immune responses to sPLA2s from different species can provide a suitable model in the study of antibody and T-cell cross-reactivity.
  
  
  METHODS
  Specific IgE, IgG1, IgG4, and IgA antibodies were analyzed by ELISA against sPLA2s 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) sPLA2 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 sPLA2.
  
  
  RESULTS
  Hyperimmune and allergic individuals showed high levels of sPLA2-specific IgG4 and significant IgG4 cross-reactivity between BT, DR, and NM sPLA2s. Furthermore, IgE, IgA, and IgG1 cross-reactivities against BT, DR, and NM sPLA2s were also detectable in the range of 22.2-44.8%. Allergic patients showed significant T-cell proliferative response to NM sPLA2 together with increased IFN-γ 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 IgG4 and IgA against BT, DR, and NM sPLA2s. Human TCC spanning three major T-cell epitopes of AM sPLA2 showed minor proliferative response to NM and hGIII sPLA2s.
  
  
  CONCLUSIONS
  This study shows that T cells and antibodies may show cross-reactivity between different species without being naturally exposed to sPLA2s.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. betulasin@gmail.com
authors.forename: B A
authors.initials: BA
authors.lastname: Sin
authors.forename: M
authors.initials: M
authors.lastname: Akdis
authors.forename: J
authors.initials: J
authors.lastname: Zumkehr
authors.forename: S
authors.initials: S
authors.lastname: Bezzine
authors.forename: C
authors.initials: C
authors.lastname: Bekpen
authors.forename: G
authors.initials: G
authors.lastname: Lambeau
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001516:Bees / Q000201:enzymology; D002417:Cattle; D003429:Cross Reactions; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D054497:Phospholipases A2, Secretory / Q000737:chemistry / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012911:Snakes; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000906:Antibodies; D007132:Immunoglobulin Isotypes; D054497:Phospholipases A2, Secretory