T-cell receptor analysis in Omenn's syndrome : Evidence for defects in gene rearrangement and assembly

Patients with Omenn's syndrome have a form of severe immune deficiency that is associated with pathological features of graft-versus-host disease, except for the lack of foreign engraftment. It has been hypothesized that the disease's unique clinical features are mediated by an expanded po...

Full description

Saved in:
Bibliographic Details
Published in:Blood 1999, Vol.93 (1), p.242-250
Main Authors: BROOKS, E. G, FILIPOVICH, A. H, PADGETT, J. W, MAMLOCK, R, GOLDBLUM, R. M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Biological and medical sciences
Chromosomes, Human, Pair 22 - genetics
DiGeorge Syndrome - genetics
DiGeorge Syndrome - immunology
Female
Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Gene Rearrangement, T-Lymphocyte
Humans
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunopathology
Infant
Infant, Newborn
Male
Medical sciences
Molecular Sequence Data
Receptors, Antigen, T-Cell - analysis
Receptors, Antigen, T-Cell - genetics
Severe Combined Immunodeficiency - genetics
Severe Combined Immunodeficiency - immunology
Syndrome
Transcription, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Patients with Omenn's syndrome have a form of severe immune deficiency that is associated with pathological features of graft-versus-host disease, except for the lack of foreign engraftment. It has been hypothesized that the disease's unique clinical features are mediated by an expanded population of autologous self-reactive T cells of limited clonality. In the current study, an investigation of the T-cell receptor (TCR) repertoire was undertaken to identify defects in T-cell rearrangement and development. The TCR repertoire in this group of patients was exquisitely restricted in the number of different TCR clonotypes, and some of these clonotypes seemed to have similar recognition motifs in the antigen-binding region, indicating antigen-driven proliferation of T lymphocytes. The TCRs from some patients lacked N- or P-nucleotide insertions and used proximal variable and joining gene segments, suggesting abnormal intrathymic T-cell development. Finally, abnormal assembly of gene segments and truncated rearrangements within nonproductive alleles suggested abnormalities in TCR rearrangement mechanisms. Overall, the findings suggest that inefficient and/or abnormal generation of TCRs may be a consistent feature of this disease.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.v93.1.242