ArticleThe Journal of clinical investigation2019
Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.Nature immunology · 2026Article
- Thymic selection of the T cell receptor repertoire is biased toward autoimmunity in females.eLife · 2026Article
- A Donor T-Cell Receptor Structural Signature Determines Alloreactive Potential and Predicts Acute Graft-Versus-Host Disease.bioRxiv : the preprint server for biology · 2026Article
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- TCRcloud: a global visualization tool for T-cell and B-cell receptor transcripts.Journal of translational medicine · 2026Article
- TCR repertoire shaping of naïve T cell subsets in human ontogeny.Frontiers in immunology · 2026Article
- Hydrophobic complementarity-determining region 3 (CDR3) sequences elucidate the cardiotoxic effects of immune checkpoint inhibitors.Research square · 2025Article
- Closing the Gap Between Vision and Victory in Type 1 Diabetes: The NIDDK Human Islet Research Network (HIRN) Initiative.Diabetes · 2025Review
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Age-Related Dynamics and Spectral Characteristics of the TCRβ Repertoire in Healthy Children: Implications for Immune Aging.Aging cell · 2025Article
- Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
- Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.Frontiers in immunology · 2023Article
- Two types of human TCR differentially regulate reactivity to self and non-self antigens.iScience · 2022Article
- Human stem cell-derived thymic epithelial cells enhance human T-cell development in a xenogeneic thymus.The Journal of allergy and clinical immunology · 2022Article
- Repertoire analyses reveal T cell antigen receptor sequence features that influence T cell fate.Nature immunology · 2022Article
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Article
- Divergent outcomes of anti-PD-L1 treatment coupled with host-intrinsic differences in TCR repertoire and distinct T cell activation states in responding versus non-responding tumors.Frontiers in immunology · 2022Article
- Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors.Frontiers in oncology · 2022Review
- Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals.JCI insight · 2021Article
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Abstract
We investigated human T-cell repertoire formation using high throughput TCRβ CDR3 sequencing in immunodeficient mice receiving human hematopoietic stem cells (HSCs) and human thymus grafts. Replicate humanized mice generated diverse and highly divergent repertoires. Repertoire narrowing and increased CDR3β sharing was observed during thymocyte selection. While hydrophobicity analysis implicated self-peptides in positive selection of the overall repertoire, positive selection favored shorter shared sequences that had reduced hydrophobicity at positions 6 and 7 of CDR3βs, suggesting weaker interactions with self-peptides than unshared sequences, possibly allowing escape from negative selection. Sharing was similar between autologous and allogeneic thymi and occurred between different cell subsets. Shared sequences were enriched for allo-crossreactive CDR3βs and for Type 1 diabetes-associated autoreactive CDR3βs. Single-cell TCR-sequencing showed increased sharing of CDR3αs compared to CDR3βs between mice. Our data collectively implicate preferential positive selection for shared human CDR3βs that are highly cross-reactive. While previous studies suggested a role for recombination bias in producing "public" sequences in mice, our study is the first to demonstrate a role for thymic selection. Our results implicate positive selection for promiscuous TCRβ sequences that likely evade negative selection, due to their low affinity for self-ligands, in the abundance of "public" human TCRβ sequences.
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