Rabbit Anti-Papain Polyclonal antibody

Background Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. Methods We screened mice carrying homozygous and heterozygousN-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. Results Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2,Prkd2,andScarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. Conclusions Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.

Cathepsins, a superfamily of hydrolytic enzymes produced and enclosed within lysosomes, play multiple roles at physiological and pathological states. Cathepsin S is a lysosomal cysteine endopeptidase of the papain family, and exerts critical roles in the regulation of MHC class II immune responses. In the present study, we captured two Cathepsin S genes in turbot (SmCTSS1 and SmCTSS2.1), characterized their expression patterns following V. anguillarum and S. iniae infections, and explored their binding ability and agglutination capability. Firstly, the SmCTSS1 contained a 990 bp ORF encoding 329 amino acids, while SmCTSS2.1 contained a 1,014 bp ORF encoding 337 amino acids. The phylogenetic analysis revealed that both genes showed the closest relationship to their counterparts of Japanese flounder (Paralichthys olivaceus). In addition, both genes were ubiquitously expressed in all examined healthy tissues, with the highest expression level observed in spleen and intestine, respectively, while the lowest expression level both observed in liver. Both SmCTSS1 and SmCTSS2.1 were significantly differentially expressed, and exhibited general down-regulations at most time points in skin and intestine after two bacterial infections. Finally, both rSmCTSS1 and rSmCTSS2.1 showed significant binding ability to three examined microbial ligands (LPS, PGN and LTA), and strong agglutination effect to different bacteria (E. tarda, S. agalactiae, S. aureus and V. anguillarum). Collectively, this study provided valuable data for understanding the roles of CTSS in the host defense against bacterial infections in turbot, and indicated the potential vital roles of CTSS in innate immune responses of teleost species.