scholarly journals Peptide-receptive Major Histocompatibility Complex Class I Molecules Cycle between Endoplasmic Reticulum andcis-Golgi in Wild-type Lymphocytes

2007 ◽  
Vol 282 (42) ◽  
pp. 30680-30690 ◽  
Author(s):  
Malgorzata Garstka ◽  
Britta Borchert ◽  
Mohammed Al-Balushi ◽  
PVK Praveen ◽  
Nicole Kühl ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Wild Type ◽  
Histocompatibility Complex

scholarly journals Requirements for the Selective Degradation of Endoplasmic Reticulum-Resident Major Histocompatibility Complex Class I Proteins by the Viral Immune Evasion Molecule mK3

2005 ◽  
Vol 79 (7) ◽  
pp. 4099-4108 ◽  
Author(s):  
Xiaoli Wang ◽  
Rose Connors ◽  
Michael R. Harris ◽  
Ted H. Hansen ◽  
Lonnie Lybarger
Keyword(s):  
Endoplasmic Reticulum ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Surface Display ◽  
Class I ◽  
Dislocation Model ◽  
Degradation Pathways ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

ABSTRACT Recent studies suggest that certain viral proteins co-opt endoplasmic reticulum (ER) degradation pathways to prevent the surface display of major histocompatibility complex class I molecules to the immune system. A novel example of such a molecule is the mK3 protein of gammaherpesvirus 68. mK3 belongs to an extensive family of structurally similar viral and cellular proteins that function as ubiquitin ligases using a conserved RING-CH domain. In the specific case of mK3, it selectively targets the rapid degradation of nascent class I heavy chains in the ER while they are associated with the class I peptide-loading complex (PLC). We present here evidence that the PLC imposes a relative proximity and/or orientation on the RING-CH domain of mK3 that is required for it to specifically target class I molecules for degradation. Furthermore, we demonstrate that full assembly of class I molecules with peptide is not a prerequisite for mK3-mediated degradation. Surprisingly, although the cytosolic tail of class I is required for rapid mK3-mediated degradation, we observed that a class I mutant lacking lysine residues in its cytosolic tail was ubiquitinated and degraded in the presence of mK3 in a manner indistinguishable from wild-type class I molecules. These findings are consistent with a “partial dislocation” model for turnover of ER proteins and define some common features of ER degradation pathways initiated by structurally distinct herpesvirus proteins.

scholarly journals The protease inhibitor, N-acetyl-L-leucyl-L-leucyl-leucyl-L-norleucinal, decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum.

1996 ◽  
Vol 183 (4) ◽  
pp. 1569-1578 ◽  
Author(s):  
E A Hughes ◽  
B Ortmann ◽  
M Surman ◽  
P Cresswell
Keyword(s):  
Endoplasmic Reticulum ◽  
Major Histocompatibility Complex ◽  
Protease Inhibitor ◽  
Major Histocompatibility Complex Class ◽  
Antigen Processing ◽  
Intracellular Transport ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

N-acetyl-L-leucyl-L-leucyl-L-norleucinal, (LLnL), which inhibits proteasomes in addition to other proteases, was found to prolong the association of major histocompatibility complex class I molecules with the transporters associated with antigen processing (TAP), and to slow their transport out of the endoplasmic reticulum (ER). LLnL induced a reversible accumulation of ubiquitinated proteins and changed the spectrum of peptides bound by class I molecules. These effects can probably be attributed to proteasome inhibition. Unexpectedly, in the TAP-deficient cell line .174, the rate of intracellular transport of human histocompatibility leukocyte antigen (HLA) A2 was also reduced by LLnL, and the generation of most HLA-A2-associated signal sequence peptides was inhibited. The inhibition of HLA-A2 transport in .174 cells was found to be less sensitive to LLnL than in wild-type cells, and a similar difference was found for a second protease inhibitor, benzyloxycarbonyl-L-leucyl-L-leucyl-L-phenylalanilal. These data suggest that under some conditions such inhibitors can block trimming of peptides by an ER peptidase in addition to inhibiting cytosolic peptide generation.

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