Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation. Issue 1 (26th August 2015)

• Record Type: Journal Article
• Authors: Camilli, Giorgio; Cassotta, Antonino; Battella, Simone; Palmieri, Gabriella; Santoni, Angela; Paladini, Fabiana; Fiorillo, Maria Teresa; Sorrentino, Rosa
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 1(2016)
• Page Start: 121
• Page End: 130
• Publication Date: 2015-08-26
• Subjects: human leukocyte antigen-E -- NK cells -- monocytic; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.1A0415-172R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : HLA-E molecules undergo an alternative pathway of intracellular trafficking in monocyte-derived macrophages. Abstract: HLA-E is a nonclassical HLA-class I molecule whose best known role is to protect from the natural killer cells. More recently, an additional function more similar to that of classical HLA-class I molecules, i.e., antigen presentation to T cells, is emerging. However, much remains to be explored about the intracellular trafficking of the HLA-E molecules. With the use of 3 different cellular contexts, 2 monocytic cell lines, U937 and THP1, and peripheral blood monocytes, we show here a remarkable increase of HLA-E during monocyte-macrophage differentiation. This goes independently from the classical HLA-class I, the main source of HLA-E-specific peptides, which is found strongly up-regulated upon differentiation of peripheral blood monocytes but not at all in the case of U937 and THP1 cell lines. Although in all cases, there was a moderate increase of HLA-E expressed in the cell surface, lysis by natural killer cells is comparably restored by an anti-NKG2A antibody in untreated as well as in PMA-differentiated U937 cells. Instead, the great majority of the HLA-E is retained in the vesicles of the autophagy-lysosome network, where they colocalize with the microtubule-associated protein light chain 3, as well as with the lysosomal-associated membrane protein 1. We conclude that differently from the classical HLA-class I molecules, the primary destination of the newly synthesized HLA-E molecules in macrophages is, rather than the cell membrane, the intracellular autophagy-lysosomal vesicles where they are stored and where they can encounter the exogenous antigens.