Characterization of locus-specific expression of HLA class I on stem cells...

Background

Classical human leukocyte antigens (HLA) of class I act as ligand for the T-lymphocyte receptor (TcR) and the killer-cell immunoglobulin-like receptor on NK cells. HLA class I antigens are encoded by highly polymorphic genes at three closely linked loci, HLA-A, -B and -C. Through HLA molecules self and non-self peptides are presented on the cell surface to T lymphocytes or NK cells. Cytotoxic T lymphocytes recognize these peptide-HLA class I complexes and kill the presenting cell leading to elimination of tumours or infected cells. The current dogma which is presented by many authoritative text books in immunology implies that HLA class I is present on all nucleated cells in the body. This dogma is however in conflict with earlier data showing that constitutive expression of HLA class I is largely restricted to cells of the lymphoid organs, epithelial cells and the lining of small vessels i.e. a minority of the body cells.

 

Aims

The purpose is to study whether the three loci (A, B and C) are always expressed co-dominantly or they are individually regulated and even have different functions. In fact, very little is known about locus-specific HLA class I expression in normal cells.

 

Methods

Different tissues from the body will be studied using immunohistochemical staining with allele specific antibodies, whereas flow cytometry will be used to define the stage where hematopoietic lineages start to express HLA-A and -B. Furthermore, allele specific HLA expression will be compared between healthy tissue and inflamed tissue (Celiac Disease).

 

Using allele-specific HLA class I antibodies we analyzed the expression of HLA-A and HLA-B on human mesenchymal stem cells (MSC), human satellite cells and also in some differentiated cell types like smooth muscle cells and fibroblasts. We have found that surface expressions of HLA-B alleles are strongly down-regulated whereas expression of HLA-A is high on all cells studied.