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A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation (CROSBI ID 82086)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Reusch, Uwe ; Muranyi, Walter ; Lučin, Pero ; Burgert, Hans-Georg ; Hengel, Hartmut ; Koszinowski, Ulrich H. A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation // EMBO journal, 18 (1999), 4; 1081-1091-x

Podaci o odgovornosti

Reusch, Uwe ; Muranyi, Walter ; Lučin, Pero ; Burgert, Hans-Georg ; Hengel, Hartmut ; Koszinowski, Ulrich H.

engleski

A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation

Mouse cytomegalovirus (MCMV) early gene expression interferes with the major histocompatibility complex class I (MHC class I) pathway of antigen presentation. Here we identify a 48 kDa type I transmembrane glycoprotein encoded by the MCMV early gene m06, which tightly binds to properly folded beta(2)-microglobulin (beta(2)m)-associated MHC class I molecules in the endoplasmic reticulum (ER), This association is mediated by the lumenal/transmembrane part of the protein. gp48-MHC class I complexes are transported out of the ER, pass the Golgi, but instead of being expressed on the cell surface, they are redirected to the endocytic route and rapidly degraded in a Lamp-1(+) compartment, As a result, m06-expressing cells are impaired in presenting antigenic peptides to CD8(+) T cells. The cytoplasmic tail of gp48 contains two di-leucine motifs, Mutation of the membrane-proximal di-leucine motif of gp48 restored surface expression of MHC class I, while mutation of the distal one had no effect. The results establish a novel viral mechanism for down-regulation of MHC class I molecules by directly binding surface-destined MHC complexes and exploiting the cellular di-leucine sorting machinery for lysosomal degradation.

antigen presentation; cytomegalovirus; di-leucine; lysosomes; MHC class I

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Podaci o izdanju

18 (4)

1999.

1081-1091-x

objavljeno

0261-4189

Povezanost rada

Temeljne medicinske znanosti

Indeksiranost