Associations and Interactions between Bare Lymphocyte Syndrome Factors

ABSTRACT The bare lymphocyte syndrome, a severe combined immunodeficiency due to loss of major histocompatibility complex (MHC) class II gene expression, is caused by inherited mutations in the genes encoding the heterotrimeric transcription factor RFX (RFX-B, RFX5, and RFXAP) and the class II transactivator CIITA. Mutagenesis of the RFX genes was performed, and the properties of the proteins were analyzed with regard to transactivation, DNA binding, and protein-protein interactions. The results identified specific domains within each of the three RFX subunits that were necessary for RFX complex formation, including the ankyrin repeats of RFX-B. DNA binding was dependent on RFX complex formation, and transactivation was dependent on a region of RFX5. RFX5 was found to interact with CIITA, and this interaction was dependent on a proline-rich domain within RFX5. Thus, these studies have defined the protein domains required for the functional regulation of MHC class II genes.

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A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome).

Genes & Development ◽

10.1101/gad.9.9.1021 ◽

1995 ◽

Vol 9 (9) ◽

pp. 1021-1032 ◽

Cited By ~ 237

Author(s):

V Steimle ◽

B Durand ◽

E Barras ◽

M Zufferey ◽

M R Hadam ◽

...

Keyword(s):

Dna Binding ◽

Mhc Class Ii ◽

Class Ii ◽

Regulatory Factor ◽

Bare Lymphocyte Syndrome ◽

Mhc Class Ii Deficiency

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Impact of negatively charged patches on the surface of MHC class II antigen-presenting proteins on risk of chronic beryllium disease

Journal of The Royal Society Interface ◽

10.1098/rsif.2007.1223 ◽

2007 ◽

Vol 5 (24) ◽

pp. 749-758 ◽

Cited By ~ 20

Author(s):

James A Snyder ◽

Eugene Demchuk ◽

Erin C McCanlies ◽

Christine R Schuler ◽

Kathleen Kreiss ◽

...

Keyword(s):

Glutamic Acid ◽

Mhc Class Ii ◽

Protein Interactions ◽

Class Ii ◽

Chronic Beryllium Disease ◽

Glutamic Acid Residue ◽

The One ◽

Class Ii Antigen ◽

Antigen Presenting ◽

Beryllium Disease

Chronic beryllium disease (CBD) is a granulomatous lung disease that occurs primarily in workers who are exposed to beryllium dust or fumes. Although exposure to beryllium is a necessary factor in the pathobiology of CBD, alleles that code for a glutamic acid residue at the 69th position of the HLA-DPβ1 gene have previously been found to be associated with CBD. To date, 43 HLA-DPβ1 alleles that code for glutamic acid 69 (E69) have been described. Whether all of these E69 coding alleles convey equal risk of CBD is unknown. The present study demonstrates that, on the one hand, E69 alleloforms of major histocompatibility complex class II antigen-presenting proteins with the greatest negative surface charge convey the highest risk of CBD, and on the other hand, irrespective of allele, they convey equal risk of beryllium sensitization (BeS). In addition, the data suggest that the same alleles that cause the greatest risk of CBD are also important for the progression from BeS to CBD. Alleles convey the highest risk code for E26 in a constant region and for E69, aspartic acid 55 (D55), E56, D84 and E85 in hypervariable regions of the HLA-DPβ1 chain. Together with the calculated high binding affinities for beryllium, these results suggest that an adverse immune response, leading to CBD, is triggered by chemically specific metal–protein interactions.

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HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells

Nature ◽

10.1038/368554a0 ◽

1994 ◽

Vol 368 (6471) ◽

pp. 554-558 ◽

Cited By ~ 193

Author(s):

Steven P. Fling ◽

Benjamin Arp ◽

Donald Pious

Keyword(s):

Complex Formation ◽

Mhc Class Ii ◽

Antigen Presenting Cells ◽

Class Ii ◽

Peptide Complex ◽

Antigen Presenting

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Conserved residues of the bare lymphocyte syndrome transcription factor RFXAP determine coordinate MHC class II expression

Molecular Immunology ◽

10.1016/j.molimm.2005.03.008 ◽

2006 ◽

Vol 43 (5) ◽

pp. 395-409 ◽

Cited By ~ 12

Author(s):

Alyssa B. Long ◽

Angela M. Ferguson ◽

Parimal Majumder ◽

Uma M. Nagarajan ◽

Jeremy M. Boss

Keyword(s):

Transcription Factor ◽

Mhc Class Ii ◽

Class Ii ◽

Conserved Residues ◽

Bare Lymphocyte Syndrome

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Regulation of a Graft-Versus-Leukemia Effect by Major Histocompatibility Complex Class II Molecules on Leukemia Cells: HLA-DR1 Expression Renders K562 Cell Tumors Resistant to Adoptively Transferred Lymphocytes in Severe Combined Immunodeficiency Mice/Nonobese Diabetic Mice

Blood ◽

10.1182/blood.v90.11.4553 ◽

1997 ◽

Vol 90 (11) ◽

pp. 4553-4558 ◽

Cited By ~ 10

Author(s):

Frank F. Weichold ◽

Yin-zheng Jiang ◽

Daniel E. Dunn ◽

Michael Bloom ◽

Vera Malkovska ◽

...

Keyword(s):

Mhc Class Ii ◽

Nk Cell ◽

Severe Combined Immunodeficiency ◽

Nod Mice ◽

Class Ii ◽

Leukemia Cells ◽

Combined Immunodeficiency ◽

Histocompatibility Complex ◽

Proliferation In Vitro

Abstract To understand the role of key molecules in determining the strength and nature of allogeneic T-cell response to leukemia, we transfected HLA-DR1 into the major histocompatibility complex (MHC)-deficient, natural killer (NK)-cell sensitive K562 leukemia cell line. Untransfected K562 cells stimulated NK proliferation in vitro and formed subcutaneous tumors in severe combined immunodeficiency/non-obese diabetic (SCID/NOD) mice. Tumor growth was inhibited by adoptive intravenous transfer of fresh unprimed peripheral blood mononuclear cells (PBMC). In contrast, HLA-DR1 transfected cells stimulated CD4+ T cells, but not NK-cell proliferation in vitro and formed tumors resistant to fresh PBMC in SCID/NOD mice. Tumors not expressing MHC were infiltrated with CD16+CD56+ lymphocytes whereas nonregressing HLA-DR1 expressing tumors showed only a scanty infiltration with both T-cell and NK-cell subsets. The results indicate that MHC class II expression by leukemia cells can determine the effector cell type that it engages. In vivo MHC class II expression rendered K562 cell tumors resistant to NK-cell mediated antitumor reactivity.

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