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The 77C->G mutation in the human CD45 (PTPRC) gene leads to increased intensity of TCR signaling in T cell lines from healthy individuals and patients with multiple sclerosis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Jan 15; Vol. 176 (2), pp. 931-8. - Publication Year :
- 2006
-
Abstract
- The 77C-->G mutation in exon A of the human CD45 gene occurs with low frequency in healthy individuals. An enhanced frequency of 77C-->G individuals has been reported in cohorts of patients suffering from multiple sclerosis, systemic sclerosis, autoimmune hepatitis, and HIV-1. To investigate the mechanisms by which the variant allele may contribute to disease susceptibility, we compared T cell reactivity in heterozygous carriers of the mutation (healthy individuals and multiple sclerosis patients) and wild-type controls. In vitro-generated T cell lines and freshly isolated CD4+CD45R0+ primed/memory T cells from 77C-->G individuals aberrantly expressed CD45RA isoforms and showed enhanced proliferation and IL-2 production when stimulated with anti-TCR/CD3 mAb or Ag. Mutant T cell lines contained a more active pool of p56lck tyrosine kinase and responded with increased phosphorylation of Zap70 and TCR-zeta and an enhanced Ca2+ flux to TCR/CD3 stimulation. These data suggest that 77C-->G may act as a risk factor for certain diseases by increasing the intensity of TCR signaling.
- Subjects :
- Antibodies, Monoclonal pharmacology
Base Sequence
Case-Control Studies
Cell Line
DNA genetics
Heterozygote
Humans
Immunologic Memory
In Vitro Techniques
Isoantigens administration & dosage
Signal Transduction
Leukocyte Common Antigens genetics
Multiple Sclerosis genetics
Multiple Sclerosis immunology
Point Mutation
Receptors, Antigen, T-Cell metabolism
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 176
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 16393978
- Full Text :
- https://doi.org/10.4049/jimmunol.176.2.931