Globular-shaped variable lymphocyte receptors B antibody multimerized by a hydrophobic clustering in hagfish

Citation

Kim J, Im SP, Lee JS, Lazarte JMS, Kim SW, Jung JW, Kim JY, Kim YR, Lee S, Kim GJ, Jung HS, Lee KO, Adams A, Thompson KD & Jung TS (2018) Globular-shaped variable lymphocyte receptors B antibody multimerized by a hydrophobic clustering in hagfish. Scientific Reports, 8, Art. No.: 10801. https://doi.org/10.1038/s41598-018-29197-w

Abstract
In hagfish and lampreys, two representative jawless vertebrates, the humoral immunity is directly mediated by variable lymphocyte receptors B (VLRBs). Both monomeric VLRBs are structurally and functionally similar, but their C-terminal tails differ: lamprey VLRB has a Cys-rich tail that forms disulfide-linked pentamers of dimers, contributing to its multivalency, whereas hagfish VLRB has a superhydrophobic tail of unknown structure. Here, we reveal that VLRBs obtained from hagfish plasma have a globular-shaped multimerized form (approximately 0.6 to 1.7 MDa) that is generated by hydrophobic clustering instead of covalent linkage. Electron microscopy (EM) and single-particle analysis showed that the multimerized VLRBs form globular-shaped clusters with an average diameter of 28.7 ± 2.2 nm. The presence of VLRBs in the complex was confirmed by immune-EM analysis using an anti-VLRB antibody. Furthermore, the hydrophobic hagfish C-terminus (HC) was capable of triggering multimerization and directing the cellular surface localization via a glycophosphatidylinositol linkage. Our results strongly suggest that the hagfish VLRB forms a previously unknown globular-shaped antibody. This novel identification of a structurally unusual VLRB complex may suggest that the adaptive immune system of hagfish differs from that of lamprey.

Journal
Scientific Reports: Volume 8

• Published version