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Universal Cells Inc.
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  5. HLA Class II Engineering

HLA Class II Engineering

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The HLA Class II molecules DP, DQ and DR present peptides to CD4+ T cells and are composed of polymorphic alpha and beta chains. All Class II molecules are expressed from promoters that require the same set of transcription factors. Mutations in the transcription factors RFX5, RFXANK, RFXAP, or CIITA prevent HLA class II expression and cause Bare Lymphocyte Syndrome. Universal Donor Cells can be engineered to lack one of these factors. The single chain HLA-E molecule produced by class I engineering is still expressed.
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HLA class II molecules are expressed on antigen presenting cells such as dendritic cells, macrophages and B cells, and many other cell types upregulate their expression in response to inflammation and other signals. Unlike HLA class I, class II proteins lack a common subunit that can be edited to prevent surface expression. Instead, Universal Cells edits one of the four transcription factor genes required for all class II gene expression (CIITA, RFXANK, RFX5, RFXAP). Bare Lymphocyte Syndrome patients with mutations in these genes do not express class II molecules on their antigen presenting cells, but are otherwise normal. Combining class I and class II engineering creates universal donor stem cell lines that are appropriate for deriving many differentiated cell products.