Evolution of immunogenetic components used to form ultralong VH CDR3 antibodies in Bovidae
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AbstractCattle has a restricted repository of immunoglobulin heavy chain gene segments with only one family of V, 4 J and 16 D segments functional. Among these segments are a V and D that, together, encode a heavy chain with an ultralong CDR3 region which manifests as a stalk supporting a knob domain of which only the knob has antigen binding capability. This antibody structure has boundless therapeutic potential, including for treatment of HIV and other antigens with veiled epitopes. Upon the discovery of this ultralong antibody in Bos taurus, speculation of its origin began. The components that should facilitate ultralong CDR3H antibodies appear in more species than just Bos taurus; they expand throughout the bovine subfamily as evidence by the presence of a V motif TTVHQ crested by an 8 base-pair (bp) duplication, and a comparatively long D segment. Several closely-related species encode the ultralong V segments gene in their germline IgH locus. Phylogenetically bookending the cluster that is genomically equipped for the ultralong cattlebody are the species Bos taurus and Bison bison with Bos mutus, indicus, and grunniens in between. The added length of the D segment is less consistent throughout the group as none of the species encode as long of segment as Bos taurus at 50 amino acids. Two species studied, Bos mutus and Bos grunniens, have 15 and 22 amino acids, respectively, encoded by their longest D segment, and Bison bison has 23. Though we do know the germline encodes the ultralong antibody, it is imperative to know if the gene rearrangement is actually expressed and employed in the mature repertoire.
Mitchell, C. D., Marchand, A. J., Head, K., Haakenson, J. K., Kelley, A., Deiss, T. C., ... Criscitiello, M. F.
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Mitchell, Christian D||Marchand, Ashley J||Head, Kelly||Haakenson, Jeremy K||Kelley, Abigail||Deiss, Thaddeus C||Derr, James N||Smider, Vaughn V||Criscitiello, Michael F
