Aberant confirmations of HLA-B27 in ankylosing spondylitis

Project: Research

Description

MHC-I is a family of proteins that presents antigenic peptides to cells of our immune defense. Alterations, either in the quality or quantity, trigger immune reactions from cytotoxic T cells or NK cells. There are three classical MHC-I genes with together over 7000 different alleles (i.e., these are actually the most polymorphic genes that exist). These genes code for functional MHC-I proteins (MHC-I allomorphs). This diversity of MHC-I is crucial for the organism and population to be able to respond to all kinds of viral infections. The non-polymorphic protein tapasin is a key regulator of both quality and quantity of MHC-I molecules.1 Without tapasin the expression and hence antigen presenting capacity of MHC-I is severely impaired. Tapasin is of high medical relevance since tapasin and MHC-I molecules are dysregulated in many types of tumors and we have recently found that tapasin also strongly affects abberant conformations of certain MHC-I molecules (HLA-B27) found in the inflammatory disease ankylosing spondylitis. Interestingly the amount of abberant conformations of MHC-I is affected by pH and so is the effect of tapasin (unpublished data). Morever, we have also recent data showing that recombinant tapasin can be used to reduce the amount of abberant conformations, which could be a potential new complementary way to treat patients with ankylosing spondylitis.
In this project we use circular dichroism and different scattering techniques to study tapasin solution structure as a function of pH, cellular models to study how recombinant tapasin can be used to modulate the different conformations and expression of HLA-B27 on cells, and biochemical assays to study aggregation and conformations of HLA-B27.
Short titleB27 in AS
StatusActive
Effective start/end date2014/07/01 → …

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