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Updated: Jul 10, 2026
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Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery
Published on: October 4, 2018
Allelic variant in CTLA4 alters T cell phosphorylation patterns
Lisa M Maier1, David E Anderson, Philip L De Jager
1Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Summary
Common autoimmune disease variants can alter T cell signaling. The CT60 (rs3087243) gene variant affects T cell receptor signaling in both naive and memory T cells, impacting autoimmune disease susceptibility.
Area of Science:
- Immunology
- Genetics
Background:
- Common autoimmune susceptibility variants' functional effects on human immune cells are largely unknown.
- The CT60 single nucleotide polymorphism (SNP) (rs3087243; A/G) in the CTLA4 gene's 3' UTR is linked to autoimmune diseases.
Purpose of the Study:
- To investigate the functional consequences of allelic variation in the CTLA4 gene on T cell signaling in healthy individuals.
- To determine if the CT60 genotype influences T cell antigen receptor (TCR) signaling pathways in naive and memory T cells.
Main Methods:
- Analysis of a cohort of healthy individuals stratified by CTLA4 genotypes.
- Utilizing phospho-site-specific monoclonal antibodies (mAbs) to assess T cell signaling.
- Quantifying downstream signaling molecule phosphorylation levels following TCR stimulation, normalized to CD3zeta signaling.
Main Results:
- The CT60 genotype at CTLA4 was associated with altered relative responsiveness to TCR stimulation in both naive (CD4+CD45RAhigh) and memory (CD4+CD45RAlow) T cells.
- Individuals carrying the disease-susceptibility allele at CTLA4 exhibited modified T cell signaling thresholds.
Conclusions:
- Allelic variation in genes associated with autoimmune diseases, such as CTLA4, can modulate the signaling threshold of CD4+ T cells.
- This study presents a framework for dissecting the role of T cell susceptibility genes in the pathogenesis of autoimmune diseases.
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