Molecular analysis of HLA class I and class II antigen loss mutants reveals a homozygous deletion of the DR, DQ, and part of the DP region: Implications for class II gene order

Erlich, Henry A.; Lee, J.S.; Petersen, Jean W.; Bugawan, T.; DeMars, R

doi:10.1016/0198-8859(86)90049-2

Cited by 58 publications

(28 citation statements)

References 26 publications

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“…The lymphoblastoid cell lines 721 and 721.174 have been previously described (34). Line 721 expresses mainly immunoproteasome complexes, whereas line 721.174 harbors exclusively housekeeping proteasome complexes; similar cleavage profiles have been observed for the two proteasome types (not shown).…”

Section: Methodsmentioning

confidence: 57%

Identification of Naturally Processed HLA-A2—Restricted Proinsulin Epitopes by Reverse Immunology

et al. 2005

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Type 1 diabetes is thought to result from the destruction of ␤-cells by autoantigen-specific T-cells. Observations in the NOD mouse model suggest that CD8 ؉ cytotoxic T-cells play an essential role in both the initial triggering of insulitis and its destructive phase. However, little is known about the epitopes derived from human ␤-cell autoantigens and presented by HLA class I molecules. We used a novel reverse immunology approach to identify HLA-A2؊restricted, naturally processed epitopes derived from proinsulin, an autoantigen likely to play an important role in the pathogenesis of type 1 diabetes. Recombinant human proinsulin was digested with purified proteasome complexes to establish an inventory of potential COOH-terminals of HLA class I؊presented epitopes. Cleavage data were then combined with epitope predictions based on the SYF PEITHI and BIMAS algorithms to select 10 candidate epitopes; 7 of these, including 3 with a sequence identical to murine proinsulin, were immunogenic in HLA-A2 transgenic mice. Moreover, six of six tested peptides were processed and presented by proinsulin-expressing cells. These results demonstrate the power of reverse immunology approaches. Moreover, the novel epitopes may be of significant interest in monitoring autoreactive T-cells in type 1 diabetes.

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Section: Methodsmentioning

confidence: 57%

Identification of Naturally Processed HLA-A2—Restricted Proinsulin Epitopes by Reverse Immunology

et al. 2005

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“…The 781.82 cell line has a large deletion of the HLA-I and HLA-II regions on one chromosome and a deletion of the HLA-DR, -DQA1, and -DQB1 genes on the other one (19,20). All cell lines were grown in RPMI 1640 supplemented with 10% FCS, penicillin, and streptomycin, except for HeLa cells that were grown in DMEM (all media from Invitrogen, Fisher Scientific, Illkirch Graffenstaden, France).…”

Section: Cell Linesmentioning

confidence: 99%

HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule

Lenormand

Bausinger

Gross

et al. 2012

The Journal of Immunology

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The precise role of human epidermal Langerhans cells (LCs) in immune response is highly controversial. While studying the gene expression profile of these cells, we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs. Despite a strong evolutionary conservation of their sequences, the concomitant expression of the poorly polymorphic HLA-DQA2/HLA-DQB2 genes, paralogous to the HLA-DQA1/HLA-DQB1 genes, has never been detected in any cell type. We confirmed by RT-PCR that the HLA-DQA2 and -DQB2 genes are both expressed in LCs, but not in monocyte-derived dendritic cells, or in blood CD1c+ or plasmacytoid dendritic cells. The presence of the HLA-DQβ2 chain in LCs could be demonstrated by Western blotting, whereas immunofluorescence revealed its localization in early endosomes. As in the case of other HLA class II molecules, the HLA-DQα2 and -DQβ2 chains formed heterodimers that had to associate with the invariant chain to reach endosomal compartments. HLA-DQα2/β2 heterodimers were expressed at the cell surface, where they could mediate staphylococcal superantigen stimulation of T cells. Interestingly, HLA-DQα2 and HLA-DQβ1 chains formed mixed heterodimers which efficiently left the endoplasmic reticulum. These observations strongly suggest that the poorly polymorphic HLA-DQA2 and -DQB2 genes should be considered to be of immunological importance. The HLA-DQα2/β2 molecules could influence the complexity of the repertoire of Ags presented by LCs.

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“…We then expressed the DQ α1/β1 heterodimers in a human LCL line, 721.174, and infected the cells with recombinant EBV (293-EBV) that encodes a hygromycin-resistance gene (27). 721.174 cells have a deletion in HLA-DQ, -DR, and part of -DP (28). EBV infectivity was measured by real-time RT-qPCR detecting the copy number of hygromycin-resistance gene mRNA normalized against the copy number of GAPDH mRNA amplified in the same reaction as an internal control.…”

Section: Resultsmentioning

confidence: 99%

HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells

Li¹,

Bu²,

Gabriel³

et al. 2017

JCI Insight

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Molecular analysis of HLA class I and class II antigen loss mutants reveals a homozygous deletion of the DR, DQ, and part of the DP region: Implications for class II gene order

Cited by 58 publications

References 26 publications

Identification of Naturally Processed HLA-A2—Restricted Proinsulin Epitopes by Reverse Immunology

Identification of Naturally Processed HLA-A2—Restricted Proinsulin Epitopes by Reverse Immunology

HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule

HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells

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