Characterization of Binding of LILRA3 and LILRB2 to the Myelin-Associated Inhibitors and Major Histocompatibility Class I Molecules

• Author / Creator

  Morcos, Chris

• The leukocyte immunoglobulin-like receptor family (LILR) is composed of inhibitory and activating receptors that are widely expressed on immune cells and interact with classical and non-classical MHC-I. Recently, several ligands have been identified for the LILRs including the three myelin-associated inhibitors (MAI): Nogo, MAG and OMgp. We hypothesize that the interaction between the LILRs and the MAIs modulate their interaction with MHC-I, and the interactions involve them in CNS immune-mediated diseases such as multiple sclerosis. We set out to characterize the interactions of the LILRs with the MAIs in multiple assays. LILRA3 and LILRB2 showed modest binding to OMgp in a direct ELISA and a cell-based flow cytometry assay. We attempted to block the binding to OMgp by pre-treating LILRA3 and LILRB2 with Nogo66, a 66 amino acid domain common to all Nogo isotypes. This however resulted in the enhancement of the interaction between the LILRs and OMgp. The binding between the LILRs and MHC-I was also enhanced when the LILRs were pre-incubated with Nogo66. Further experimentation is required to understand the dynamics of the interaction between the LILRs and Nogo66, and how it enhances their interaction with MHC-I and OMgp. Additionally, we shall identify the specific immunoglobulin domains of the LILRs that are key to the interaction with the MAIs. The interaction of the LILRs with Nogo and the widespread expression of Nogo-B suggest there may be context dependent roles for the LILRs beyond the expected immune regulatory function.

• Subjects / Keywords

  • Immunology
  • LILRA3
  • LILRB2
  • Leukocyte Ig-Like Receptors
  • Nogo
  • LILR
  • OMgp

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3S46HN87

• License

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