|
|
| J. Immunol. Jan (1998); 160(1):171-9 | |
| Reduced cell surface expression of HLA-C molecules correlates with restricted peptide binding and stable TAP interaction. | |
| Neisig A, Melief CJ, Neefjes J | |
| Department of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam. | |
| Abstract: HLA-C molecules are poorly expressed at the cell surface compared with HLA-A and HLA-B locus products. The reason for the low surface expression and the underlying mechanism is unclear. We show that the HLA-C4 allele is expressed intracellularly in amounts similar to HLA-A and HLA-B alleles. However, the majority of the HLA-C4 molecules is not transported, but is retained in the endoplasmic reticulum by stable interaction with TAP. This pool does not appear to participate in the formation of HLA-C4/peptide complexes, but is degraded in the endoplasmic reticulum. HLA-C4 molecules can dissociate from TAP upon binding of specific peptide. However, they require a 10-fold higher concentration of a completely degenerated 9-mer peptide mixture for release from TAP than the HLA-A and HLA-B alleles. Our data show that the HLA-C molecules tested are more selective in their peptide binding than HLA-A and HLA-B molecules, resulting in prolonged association with TAP and a reduced formation of intracellular HLA-C/peptide complexes. The restricted peptide binding of certain HLA-C alleles provides one explanation for the reduced expression of HLA-C molecules at the cell surface. Other mechanisms will be discussed. | |
| [PUBMED: 9551969] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
| terms and conditions - privacy policy - Osprey Network Visualization System |
| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |