Coordinate defects in human histocompatibility leukocyte antigen class II expression and antigen presentation in bare lymphocyte syndrome

Susan Kovats, Sheila Drover, William H. Marshall, Daniel Freed, Phyllis E. Whiteley, Gerald T. Nepom, Janice Blum

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2017-2022
Number of pages6
JournalJournal of Experimental Medicine
Volume179
Issue number6
DOIs
StatePublished - Jun 1 1994
Externally publishedYes

Fingerprint

Severe Combined Immunodeficiency
Histocompatibility Antigens Class II
Antigen Presentation
HLA Antigens
MHC Class II Genes
Antigens
Epitope Mapping
Immunocompetence
Histocompatibility
Trans-Activators
Cell Fusion
HLA-DR Antigens
Helper-Inducer T-Lymphocytes
Genes
Transfection
Proteins
B-Lymphocytes
Alleles
Viruses
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Coordinate defects in human histocompatibility leukocyte antigen class II expression and antigen presentation in bare lymphocyte syndrome. / Kovats, Susan; Drover, Sheila; Marshall, William H.; Freed, Daniel; Whiteley, Phyllis E.; Nepom, Gerald T.; Blum, Janice.

In: Journal of Experimental Medicine, Vol. 179, No. 6, 01.06.1994, p. 2017-2022.

Research output: Contribution to journalArticle

Kovats, Susan ; Drover, Sheila ; Marshall, William H. ; Freed, Daniel ; Whiteley, Phyllis E. ; Nepom, Gerald T. ; Blum, Janice. / Coordinate defects in human histocompatibility leukocyte antigen class II expression and antigen presentation in bare lymphocyte syndrome. In: Journal of Experimental Medicine. 1994 ; Vol. 179, No. 6. pp. 2017-2022.
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