Dataset Information

The contained self-reactive peripheral T cell repertoire: size, diversity and cellular composition

ABSTRACT: To further characterize the self-reactive T cell population and determine if there are sub-compartments within the naïve T cell pool that are more likely to respond in the absence of Treg cell-mediated control, we focused on CD5. CD5 is a membrane protein that is associated with the TCR and its expression is correlated with higher signaling intensity, presumably due to higher TCR self-MHC/peptide affinity, during positive selection. FACS was used to purify three distinct populations of naïve CD4+ T cells from the bottom, middle and top 10 percent based on CD5 expression; CD5low, CD5int and CD5high.

ORGANISM(S): Mus musculus

PROVIDER: GSE70154 | GEO | 2015/08/04

SECONDARY ACCESSION(S): PRJNA287757

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Atherosclerosis is a major pathological condition that underlies many cardiovascular diseases (CVDs). Its etiology involves breach of tolerance to self, leading to clonal expansion of autoreactive apolipoprotein B (APOB)–reactive CD4+T cells that correlates with clinical CVD. The T-cell receptor (TCR) sequences that mediate activation of APOB-specific CD4+T cells are unknown. Methods: In a previous study, we had profiled the hypervariable complementarity determining region 3 (CDR3) of CD4+T cells that respond to six immunodominant APOB epitopes in most donors. Here, we comprehensively analyze this dataset of 149,065 APOB-reactive and 199,211 non-reactive control CDR3s from six human leukocyte antigen–typed donors. Results: We identified 672 highly expanded (frequency threshold > 1.39E-03) clones that were significantly enriched in the APOB-reactive group as compared to the controls (log10 odds ratio ≥1, Fisher’s test p < 0.01). Analysis of 114,755 naïve, 91,001 central memory (TCM) and 29,839 effector memory (TEM) CDR3 sequences from the same donors revealed that APOB+ clones can be traced to the complex repertoire of unenriched blood T cells. The fraction of APOB+ clones that overlapped with memory CDR3s ranged from 2.2% to 46% (average 16.4%). This was significantly higher than their overlap with the naïve pool, which ranged from 0.7% to 2% (average 1.36%). CDR3 motif analysis with the machine learning–based in-silico tool, GLIPHs (grouping of lymphocyte interactions by paratope hotspots), identified 532 APOB+ motifs. Analysis of naïve and memory CDR3 sequences with GLIPH revealed that ~40% (209 of 532) of these APOB+motifs were enriched in the memory pool. Network analysis with Cytoscape revealed extensive sharing of the memory-affiliated APOB+ motifs across multiple donors. We identified six motifs that were present in TCM and TEM CDR3 sequences from >80% of the donors and were highly enriched in the APOB-reactive TCR repertoire. Discussion: The identified APOB-reactive expanded CD4+T cell clones and conserved motifs can be used to annotate and track human atherosclerosis-related autoreactive CD4+T cells and measure their clonal expansion.

Dataset Information

The contained self-reactive peripheral T cell repertoire: size, diversity and cellular composition

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure