Similar cell surface expression of β2-microglobulin-free heavy chains by HLA-B27 subtypes differentially associated with ankylosing spondylitis

2005 ◽  
Vol 52 (10) ◽  
pp. 3290-3299 ◽  
Author(s):  
Miriam N. Vázquez ◽  
José A. López de Castro
Keyword(s):  
Ankylosing Spondylitis ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hla B27 ◽  
Β2 Microglobulin ◽  
Heavy Chains ◽  
Similar Cell

scholarly journals Position 97 of HLA-B, a residue implicated in pathogenesis of ankylosing spondylitis, plays a key role in cell surface free heavy chain expression

2016 ◽  
Vol 76 (3) ◽  
pp. 593-601 ◽  
Author(s):  
Liye Chen ◽  
Hui Shi ◽  
Jack Yuan ◽  
Paul Bowness
Keyword(s):  
Ankylosing Spondylitis ◽  
Cell Surface ◽  
Heavy Chain ◽  
Protein Interactions ◽  
Hela Cells ◽  
Antigen Processing ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Expression Levels ◽  
Free Heavy Chain

ObjectiveAssociation of position 97 (P97) residue polymorphisms in human leucocyte antigen (HLA)-B, including HLA-B*27, with ankylosing spondylitis (AS) has recently been reported. We studied the effect of P97 variations on cell surface expression of the AS-associated HLA-B*27 and HLA-B*51, and the AS-protective HLA-B*7.MethodsFlow cytometry was used to measure surface expression of HLA-B*27 in C1R/HeLa cells expressing HLA-B*27 (N97) and six mutants at P97 (N97T, N97S, N97V, N97R, N97W and N97D). Transporter associated with antigen processing-deficient T2, tapasin-deficient 220, β2m-deficient HCT15 and endoplasmic reticulum aminopeptidase 1 or β2m-clustered regularly interspaced short palindromic repeats/Cas9-knockout HeLa cells were used to provide evidence for specific protein interactions. Surface expression of HLA-B*7/HLA-B*51 P97 mutants was also studied.ResultsMutation of HLA-B*27 P97 to the AS risk residue threonine increased cell surface free heavy chain (FHC) expression. Protective residues (serine or valine) and non-AS-associated residues (arginine or tryptophan) did not alter FHC expression. The N97D mutation reduced expression of conventional and FHC forms of HLA-B*27. Differences in FHC expression levels between HLA-B*27, HLA-B*27-N97T and HLA-B*27-N97D were dependent on the presence of functional β2m. HLA-B*7, which has an AS-protective serine at P97, expressed lower levels of FHC than HLA-B*27 or HLA-B*51. Introduction of asparagine at P97 of both HLA-B*7 and HLA-B*51 increased FHC expression.ConclusionsThe nature of P97 residue affects surface expression of HLA-B*27, B*7 and B*51, with AS-associated residues giving rise to higher FHC expression levels. The association of P97 amino acid polymorphisms with AS could be, at least in part, explained by its effect on HLA-B*27 FHC cell surface expression.

scholarly journals Abrogation of cell surface expression of human class I transplantation antigens by an adenovirus protein in Xenopus laevis oocytes.

1985 ◽  
Vol 101 (2) ◽  
pp. 540-547 ◽  
Author(s):  
L Severinsson ◽  
P A Peterson
Keyword(s):  
Cell Surface ◽  
Heavy Chain ◽  
Viral Protein ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Xenopus Laevis Oocytes ◽  
Human Class ◽  
Heavy Chains ◽  
Transplantation Antigens

Class I transplantation antigens form complexes with a virus protein encoded in the early region E3 of the adenovirus-2 genome. The interaction between this viral glycoprotein, E19, and nascent human class I antigens has been examined by microinjecting purified mRNA into Xenopus laevis oocytes. Both E19 and the two class I antigen subunits, the heavy chain and beta 2-microglobulin (beta 2M), were efficiently translated. The heavy chains did not become terminally glycosylated, as monitored by endoglycosidase H digestion, and were not expressed on the oocyte surface unless they were associated with beta 2M. The E19 protein did not become terminally glycosylated, and we failed to detect this viral protein on the surface of the oocytes. Co-translation of heavy chain and E19 mRNA demonstrated that the two proteins associate intracellularly. However, neither protein appeared to be transported to the trans-Golgi compartment. Similar observations were made in adenovirus-infected HeLa cells. Heavy chains bound to beta 2M became terminally glycosylated in oocytes in the presence of low concentrations of E19. At high concentrations of the viral protein, no carbohydrate modifications and no cell surface expression of class I antigens were apparent. Thus, beta 2M and E19 have opposite effects on the intracellular transport of the heavy chains. These data suggest that adenovirus-2 may impede the cell surface expression of class I antigens to escape immune surveillance.

β2-Microglobulin required for cell surface expression of blastocyst MHC

2005 ◽  
Vol 332 (1) ◽  
pp. 311-317 ◽  
Author(s):  
Toshitaka Tanaka ◽  
Tomohiko Ebata ◽  
Atsushi Tajima ◽  
Katsuyuki Kinoshita ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Β2 Microglobulin

scholarly journals Cell surface expression of HLA-E: interaction with human β2-microglobulin and allelic differences

1999 ◽  
Vol 29 (2) ◽  
pp. 537-547 ◽  
Author(s):  
Matthias Ulbrecht ◽  
Andrea Couturier ◽  
Silvia Martinozzi ◽  
Marika Pla ◽  
Rakesh Srivastava ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Β2 Microglobulin ◽  
Allelic Differences

scholarly journals MHC Class I-Like MILL Molecules Are β2-Microglobulin-Associated, GPI-Anchored Glycoproteins That Do Not Require TAP for Cell Surface Expression

2006 ◽  
Vol 177 (5) ◽  
pp. 3108-3115 ◽  
Author(s):  
Mizuho Kajikawa ◽  
Tomohisa Baba ◽  
Utano Tomaru ◽  
Yutaka Watanabe ◽  
Satoru Koganei ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Β2 Microglobulin

scholarly journals Rescue of Daudi cell HLA expression by transfection of the mouse beta 2-microglobulin gene.

1988 ◽  
Vol 167 (2) ◽  
pp. 288-299 ◽  
Author(s):  
R H Seong ◽  
C A Clayberger ◽  
A M Krensky ◽  
J R Parnes
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Daudi Cell ◽  
Heavy Chains ◽  
Daudi Cells ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Hla Molecules

The Daudi cell line is a B-lymphoblastoid line derived from a Burkitt lymphoma. Daudi cells lack cell surface expression of class I HLA molecules despite the presence of intracellular class I heavy chains. They have a defect in the gene encoding beta 2-microglobulin (beta 2m), resulting in lack of translatable mRNA for this protein. It has been thought that this deficiency is responsible for the lack of cell surface class I expression. However, data have recently been presented demonstrating that at least one mouse class I heavy chain can be expressed on the cell surface in the absence of beta 2m. These results raised the questions of whether the lack of beta 2m is the only defect in Daudi and whether transfer of this single gene could restore surface class I expression. We found that transfection of the mouse beta 2m gene into Daudi indeed rescued cell surface expression of class I HLA molecules, and that these molecules could be recognized both by monomorphic and allospecific mAbs. CTL clones specific for HLA-B17 or a determinant shared by HLA-B17 and HLA-A2 killed the Daudi cells transfected with the beta 2m gene, but not untransfected Daudi or Daudi transfected with vector alone. Mouse beta 2m on the transfected Daudi cells could exchange with human beta 2m when the cells were incubated in human serum. This exchange did not alter the ability of the cells to be killed by the specific CTLs. These results demonstrate that the lack of beta 2m is the sole reason for lack of surface class I molecules in Daudi cells, and that beta 2m is required for cell surface expression of the specific class I heavy chains of Daudi.

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