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Structural and molecular studies of group II leukocyte immunoglobulin-like receptors.

Garner, Lee Ian (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

The Leukocyte Immunoglobulin-Like Receptors (LILRs) are a family of immunomodulatory transmembrane receptors with both activatory and inhibitory forms, and are primarily expressed on myelomonocytic cells. Group I LILRs include the well-characterised members LILRB1 and LILRB2, which bind MHC Class I and transduce inhibitory signals. Group II LILRs, by comparison, are poorly understood. Particular interest has arisen in the Group II receptor, LILRB4, and its role in the induction of immune tolerance via its actions upon dendritic cells and T cells. I attempted ligand-identification and structural studies on LILRB4. Staining of human PBMCs with multimeric LILRB4 revealed broad expression of the ligand, and upregulation on activated T cells. Investigations into candidate ligands by surface plasmon resonance excluded binding to known costimulatory receptors of the B7/CD28 families. X-ray crystallographic studies revealed LILRB4 has structural similarities to LILRA5, has novel structural features at the interdomain interface, is electrostatically and chemically unsuited to the recognition of MHC Class I, and identified potential ligand interaction sites. Finally, investigations were conducted into the structure and ligand recognition of other Group II LILRs. These studies define the distribution of the LILRB4 ligand and represent the first structural analysis of this important immunoregulatory receptors.

Type of Work:Ph.D. thesis.
Supervisor(s):Willcox, Benjamin
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
ID Code:1445
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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