NETRAD_HLA

Hypothesis: anti-HLA antibodies are NOT generated by exposure to mismatched HLA antigens, but are generated from viral coinfection (likely superinfection) with EBV + a distinct virus. Exosomes/viral components including viral attachment envelope proteins that exhibit neoepitopes are released under metabolic stress (as a result of SUMOylation and deglycosylation). The NETRAD algorithm is thoroughly described in "The Origins of Allograft Rejection" (pending publication in Human Immunology, Elsevier). During antigen presentation in regional lymph nodes, the germinal center light zone is more susceptible to oxygen deprivation and stress, facilitating slower antigen presentation of immune complexes via the neonatal Fc receptor (FcRn). Upregulation of L-lysozyme, among other lysosomal enzymes, enables the digestion and loading of deglycosylated peptides onto HLA to facilitate the recognition of neoepitopes. HLA-homologous peptide motifs were generated by the Smith-Waterman algorithm. This data consists of an MS Excel spreadsheet and MS Word document with accumulated peptide motifs demonstrating homologous amino acid sequence motifs between HLA and distinct virus pairs. Combinations of 6 peptides (including N-glycan signatures) can be mapped to HLA-specific epitopes.