Post-translational cleavage generates shortened IgY forms in the snake Elaphe taeniura

While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates, the constant regions of immunoglobulin heavy chains also employ certain mechanisms to produce diversity, including class switch recombination (CSR), subclass differentiation, and different expression forms derived from the same gene. Many species of birds, reptiles and amphibians express a truncated isoform of IgY, designated as IgY(Fc), lacking the υCH3 and υCH4 domains. In Anseriformes, IgY(Fc) is generated by using different transcriptional termination sites within the same  gene. However, in some turtles, intact IgY and IgY(Fc) are respectively encoded by distinct genes. Different from the previously reported IgY(Fc), in this study, we found that the shortened IgY of the snake Elaphe taeniura is characterized by only missing a portion of CH4 domain. Using Western blotting and LC-MS/MS, we demonstrated that the truncated form of snake IgY is generated by post-translational cleavage at N338 of the IgY heavy chain constant region. We also observed that both the human and snake asparaginyl endopeptidase (AEP) can cleave snake IgY in vitro. This study reveals a novel mechanism for production of shortened IgY forms, showing that the immunoglobulin heavy chain constant region can be diversified through different strategies in vertebrates.