Authors Comment: HLA and Proteasome Expression Map

Insight into the human HLA expression pattern opens up new ways of improving cancer vaccine development

The human leukocyte antigen system (HLA system) is a group of genes that are central to the function of the immune system. These protein complexes can be found either on almost all cells (HLA class I complex) or on specific, professional antigen-presenting cells (HLA class II complex) and serve to present antigen to T cells. There is increasing evidence that pathogenic cells produce HLA class I and class II molecules either poorly or not at all, in order to escape elimination by the immune system. Recent research by bioinformaticians at TRON provides new insights into cell defense mechanisms that might assist cancer cells in evading detection by the immune system.

Functional extension of the existing seq2HLA algorithm

“Our seq2HLA algorithm, published in 2015, uses standardized NGS expression data (RNA-Seq) and gives the most likely HLA class I and II locus-specific gene expression,” says Sebastian Boegel, first author of the recently published article in the journal BMC Medical Genomics. “We have now functionally expanded the algorithm so that we can now also determine non-classical HLA types and their gene expression.” In addition, the research team has determined the expression profiles of two types of proteasome (constitutive vs. immunoproteasome) of the different tissues and additionally correlated these with HLA expression. “To the best of our knowledge, the present work provides for the first time a comprehensive expression atlas of HLA class I (classical and non-classical) and class II gene loci.”

Specific interaction of the overall components is crucial

“Our results not only shed light on the cell type-specific HLA expression patterns, but also show extremely variable gene expression of the basic components of antigen processing and presentation in different cell types,” continues Sebastian Boegel. “The data suggest that a specific interaction between the components involved in antigen processing could be crucial to maintain tolerance in immune-privileged tissues, which in turn prevents immune-related diseases.”

Comprehensive expression atlas for a better understanding of immune diseases

“We assume that this newly published resource will be the starting point for new approaches in cancer research,” continues Martin Löwer, head of the bioinformatics unit at TRON. The expression atlas could be of interest e.g. when HLA dysregulation in tumor cells is studied as part of their immune defense mechanisms, or even for the selection of new target structures for cancer immunotherapy. “Above all, the strong tissue-restrictive physiological expression and its immunosuppressive functions of HLA-G makes this an interesting molecule in cancer research,” concludes Martin Löwer.

Boegel, et al. BMC Medical Genomics (2018) 11:36

 

HLA Class I and Class II Expression Body Map. NGS RNA Seq data from physiological human tissues are analyzed using the seq2HLA algorithm to determine the classical HLA class I (blue) and HLA class II (red) expression profiles.