DO beta: a new beta chain gene in HLA-D with a distinct regulation of expression.

Tonnelle, Cécile; DeMars, Robert; Long, Eric O.

doi:10.1002/j.1460-2075.1985.tb04012.x

Cited by 325 publications

(159 citation statements)

References 62 publications

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“…This is consistent with the lack of DO␤ observed in IFN-␥-induced fibroblasts (12). We also have shown that DO␤ expression is independent of CIITA in B cells, consistent with the expression of H2-O␤ in CIITA knockout mice (44).…”

Section: Discussionsupporting

confidence: 90%

“…Also, it is possible that there are additional CIITA-inducible genes that are expressed in APCs in vivo. The identification of DN␣ as a CIITA-induced gene is consistent with the IFN-␥ induction of DN␣ in human fibroblasts (12) and neuroblastoma cells (55). We also have confirmed the requirement for CIITA for DN␣ expression by Northern analysis: DN␣ is induced both by exogenous CIITA expression in G3A cells and by endogenous CIITA in 2fTGH cells following IFN-␥ treatment.…”

Section: Discussionsupporting

confidence: 82%

“…It is especially intriguing that DN␣ is expressed in the absence of DO␤ in IFN-␥-induced cells (Ref. 12 and Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

“…The DN␣ protein originally was presumed to be independent from the DO heterodimer because in fibroblasts DN␣, but not DO␤, is induced by IFN-␥ (12). However, the association between the two subunits was suggested in studies examining DO localization in human B lymphoma cells.…”

mentioning

confidence: 99%

“…CIITA also is unique in that it is the only transcriptional activator known to be regulated by GTP binding (43). Though the DN␣ and DO␤ gene promoters also contain W, X, and Y boxes, expression of these genes is often incongruous with other MHC class II-associated genes (12,15,44), and whether DN␣ and DO␤ are induced by RFX or CIITA remains an open question.…”

mentioning

confidence: 99%

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Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Taxman

Cressman

Ting

2000

The Journal of Immunology

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Class II transcriptional activator (CIITA) is a master regulator of MHC class II genes, including DR, DP, and DQ, and MHC class II-associated genes DM and invariant chain. To determine the repertoire of genes that is regulated by CIITA and to identify uncharacterized CIITA-inducible genes, we used representational difference analysis. Representational difference analysis screens for differentially expressed transcripts. All CIITA-induced genes were MHC class II related. We have identified the α subunit, DNα, of the class II processing factor DO as an additional CIITA-inducible gene. Northern analysis confirmed that DNα is induced by IFN-γ in 2fTGH fibrosarcoma cells, and CIITA is necessary for high-level expression in B cells. The β subunit, DOβ, is not inducible in fibrosarcoma cells by IFN-γ or exogenous CIITA expression. Moreover, in contrast to other class II genes, DOβ expression remains high in the absence of CIITA in B cells. The promoters for DNα and DOβ contain the highly conserved WXY motifs, and, like other class II genes, expression of both DNα and DOβ requires RFX. These findings demonstrate that both DNα and DOβ are regulated by RFX. However, DNα is defined for the first time as a CIITA-inducible gene, and DOβ as a MHC class II gene whose expression is independent of CIITA.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 82%

“…It is especially intriguing that DN␣ is expressed in the absence of DO␤ in IFN-␥-induced cells (Ref. 12 and Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Taxman

Cressman

Ting

2000

The Journal of Immunology

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Altered major histocompatibility complex class II peptide loading in H2-O-deficient mice

et al. 2000

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The biosynthesis of MHC class II/peptide complexes involves classical, cell surface MHC products as well as the intracellular component H2‐M, required for the removal of invariant chain‐derived CLIP and for peptide loading. The function of another intracellular class II heterodimer, H2‐O, is the matter of some controversy. The physical association of H2‐O with H2‐M and co‐localization in class II+ vesicles suggest a related function in peptide exchange. Furthermore, the distinctive thymic distribution of H2‐O raises the possibility of a specialized role in T cell thymic selection. To investigate the role of H2‐O in vivo we generated mice carrying a targeted disruption in the H2‐Oa gene. No evidence was obtained for a defect in removal of CLIP. However, the array of endogenous peptides bound by class II was altered and a defect in antigen presentation through H2‐A to T cells was seen on the 129/Sv/C57BL/6 mixed strain background but not in 129/Sv pure strain mice. Furthermore, H2‐O‐null mice showed enhanced selection of CD4+ single positive thymocytes. The findings indicate that H2‐O interacts with H2‐M in peptide editing but that the genetic background in which H2‐O deficiency is manifest is also important. Overall, the experiments indicate that H2‐O/HLA‐DO should be regarded as neither up‐regulating nor down‐regulating the DM‐dependent release of CLIP, but as a modulator of peptide editing, determining the presenting cell type specific peptide profile able to retain stability in the class II groove.

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The Molecular Genetics of HLA‐Related Disorders

Bell

2007

Ciba Foundation Symposium 130 ‐ Molecular Approaches to Human Polygenic Disease

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DO beta: a new beta chain gene in HLA-D with a distinct regulation of expression.

Cited by 325 publications

References 62 publications

Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Altered major histocompatibility complex class II peptide loading in H2-O-deficient mice

The Molecular Genetics of HLA‐Related Disorders

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