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M9470079.TXT
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1994-07-02
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Document 0079
DOCN M9470079
TI Coordinate defects in human histocompatibility leukocyte antigen class
II expression and antigen presentation in bare lymphocyte syndrome.
DT 9409
AU Kovats S; Drover S; Marshall WH; Freed D; Whiteley PE; Nepom GT; Blum
JS; Immunology and Diabetes Programs, Virginia Mason Research Center,;
Seattle, Washington 98101.
SO J Exp Med. 1994 Jun 1;179(6):2017-22. Unique Identifier : AIDSLINE
MED/94253742
AB The human immunodeficiency, type II bare lymphocyte syndrome (BLS), has
been attributed to a defect in the transcription of class II
histocompatibility genes. Immunocompetence, as assessed by functional
exogenous antigen presentation, was not restored in immortalized B
cells, derived from a BLS patient, after transfection with HLA-DR class
II structural genes. Incubation of protein antigens, as well as
infectious virus, with DR-transfected BLS cells failed to induce
activation of antigen-specific helper T lymphocytes. Peptide antigens
were presented by class II molecules displayed on BLS cells, although
the conformation of these class II proteins was altered as indicated by
epitope mapping. This defect in antigen presentation was independent of
the specific class II DR allele transfected into BLS cells. Genetic
complementation analysis has been used with BLS cells to demonstrate
that the defect in class II gene transcription is linked to the absence
of a trans-acting factor. Similarly, functional class II dimers were
restored after in vitro fusion of cells derived from two distinct BLS
complementation groups, implying that specific transcriptional control
elements are shared by a gene critical for antigen presentation and
genes encoding HLA class II antigens. Thus, two important functionally
linked pathways of class II molecules, structural gene expression and
antigen presentation, share a common regulatory pathway defective in
BLS.
DE Alleles Amino Acid Sequence Cell Fusion Cell Line Clone Cells *Gene
Expression *Genes, MHC Class II Genes, Structural Genetic
Complementation Test Human HLA-D Antigens/*BIOSYNTHESIS Immunologic
Deficiency Syndromes/GENETICS/*IMMUNOLOGY Molecular Sequence Data
Oligopeptides/CHEMICAL SYNTHESIS/IMMUNOLOGY Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S. T-Lymphocytes/*IMMUNOLOGY Transcription,
Genetic Transfection JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).