HLA Class Ib and MICA/MICB Expression in Human Tissues and Cell Types: Reshuffling Immune Players

Abnormal expression of HLA class Ib, MICA and MICB molecules is associated with the evolution of pathological conditions and clinical settings. Here, we use RNA-sequencing data from two publicly-available projects, from different human organs and tissues and at single-cell level, to present their transcriptional expression throughout the human body, in comparison to that of HLA class Ia, HLA class II, their costimulatory molecules, and the main HLA transcription factors. Our analyses for 21 target genes reveal that median gene expression differs by orders of magnitude and that the classical/non-classical HLA distinction is not absolute for overall expression. Sixteen of the 21 target genes show correlated expressions, although careful analyses of individual expression patterns in tissues and organs highlight specificities. Tissue and organ expression patterns reveal that the lymphoid organs, lungs, and gastrointestinal tract organs display the highest expression of the HLA and HLA-related genes. At single-cell level, adipocytes, endothelial cells, and immune cells all have unexpectedly close expression patterns. The expression pattern of the 21 target genes in non-immune organs, such as the lung or colon, and in non-immune cells like adipocytes, questions the role of these organs and cell types in immune homeostasis and suggests additional, non-immune functions of these molecules. The lack of impact of the HLA transcription factors studied here on HLA regulation in non-immune tissues also supports a role for additional HLA transcription factors in these tissues. Finally, classical/non-classical HLA classification based on molecule structure and genetic polymorphism does not seem to extend to their expression.