Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome

S. Kovats, G. T. Nepom, M. Coleman, B. Nepom, W. W. Kwok, Janice Blum

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II αβ dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalJournal of Clinical Investigation
Volume96
Issue number1
StatePublished - 1995

Fingerprint

MHC Class II Genes
Antigen-Presenting Cells
Severe Combined Immunodeficiency
Phenotype
Gene Expression
Cell Line
Histocompatibility
Trans-Activators
Antigen Presentation
Transcriptional Activation
Bare lymphocyte syndrome 2
Antigens
Proteins

Keywords

  • disease
  • gene expression regulation
  • genes MHC class II
  • HLA-DR antigen
  • immunocompetence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome. / Kovats, S.; Nepom, G. T.; Coleman, M.; Nepom, B.; Kwok, W. W.; Blum, Janice.

In: Journal of Clinical Investigation, Vol. 96, No. 1, 1995, p. 217-223.

Research output: Contribution to journalArticle

@article{c7fe533443254012bb73ac9819f49f5b,
title = "Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome",
abstract = "The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II αβ dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.",
keywords = "disease, gene expression regulation, genes MHC class II, HLA-DR antigen, immunocompetence",
author = "S. Kovats and Nepom, {G. T.} and M. Coleman and B. Nepom and Kwok, {W. W.} and Janice Blum",
year = "1995",
language = "English (US)",
volume = "96",
pages = "217--223",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome

AU - Kovats, S.

AU - Nepom, G. T.

AU - Coleman, M.

AU - Nepom, B.

AU - Kwok, W. W.

AU - Blum, Janice

PY - 1995

Y1 - 1995

N2 - The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II αβ dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.

AB - The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II αβ dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.

KW - disease

KW - gene expression regulation

KW - genes MHC class II

KW - HLA-DR antigen

KW - immunocompetence

UR - http://www.scopus.com/inward/record.url?scp=0029092766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029092766&partnerID=8YFLogxK

M3 - Article

VL - 96

SP - 217

EP - 223

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -