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Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation.

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.

journal_name

J Leukoc Biol

journal_title

Journal of leukocyte biology

authors

Camilli G,Cassotta A,Battella S,Palmieri G,Santoni A,Paladini F,Fiorillo MT,Sorrentino R

doi

10.1189/jlb.1A0415-172R

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

121-30

issue

1

eissn

0741-5400

issn

1938-3673

pii

jlb.1A0415-172R

journal_volume

99

pub_type

杂志文章

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