Post-translational cleavage generates truncated 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 utilize certain mechanisms to produce diversity, including class switch recombination (CSR), subclass differentiation, and alternative expression of the same gene. Many species of birds, reptiles, and amphibians express a truncated isoform of immunoglobulin Y (IgY), termed IgY(ΔFc), which lacks the υCH3 and υCH4 domains. In Anseriformes, IgY(ΔFc) arises from alternative transcriptional termination sites within the same υ gene, whereas in some turtles, intact IgY and IgY(ΔFc) are encoded by distinct genes. Different from the previously reported IgY(ΔFc) variants, this study identified a truncated IgY in the snake Elaphe taeniura, characterized by the loss of only a portion of the CH4 domain. Western blotting and liquid chromatography-tandem mass spectrometry confirmed that this truncated IgY is generated by post-translational cleavage at N338 within the IgY heavy chain constant (CH) region. Furthermore, both human and snake asparaginyl endopeptidase were shown to cleave snake IgY in vitro. These findings reveal a novel mechanism for the production of shortened IgY forms, demonstrating that the immunoglobulin CH region undergoes diversification through distinct strategies across vertebrates.