Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596838
Title: The recognition of HLA-B27 by CD4+ T lymphocytes
Author: Boyle, L. H.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Abstract:
Studies in B27 transgenic animal models of the spondyloarthropathies (SpA) have demonstrated a requirement for HLA-B27, CD4+ T cells, and bacteria to induce arthritis. This has led to the hypothesis that CD4+ T cells, which usually interact with MHC class II molecules, might recognise HLA-B27. The aim of this thesis is to determine if an unusual interaction occurs between human CD4+ T cells and the MHC class I molecule HLA-B27. To attempt to isolate CD4+ T cells capable of interaction with HLA-B27, a co-culture system was developed using the MHC class II negative, MHC class I antigen processing defective cell line T2, transfected with HLA-B27 (T2-B27). This cell line expressed a variety of forms of B27 implicated in the pathogenesis of the SpA, including B27 heterodimers, free B27 heavy chains, and free B27 heavy chain homodimers. Co-culture of CD4+ T cells derived from the peripheral blood mononuclear cells of B27+ ankylosing spondylitis patients and B27+ healthy individuals with T2-B27 resulted in the isolation of a number of B27 specific CD4+ T cell lines and clones. Some of these CD4+ T cell lines appear to recognise forms of B27 including empty B27 heterodimers devoid of peptide, free B27 heavy chain homodimers, an epitope expressed on various forms of B27, and a B27 derived peptide expression on another MHC class I molecule. Some of these forms have been suggested to be important in the pathogenesis of the SpA. These B27 specific CD4+ T cells, which break the conventional rules of MHC restriction, may be relevant to the pathogenesis of the SpA.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.596838  DOI: Not available
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