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Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Brian D. Stadinski
Elizabeth A. Mills
Wan-Lin Lo
ResearchOpen Access07 Oct 2025
Nature Immunology

Volume: 26, P: 2256-2269
A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3⁺ T_reg cell development

T_reg cells are essential for self-tolerance. Huseby and colleagues identify multiple de facto T_reg cell self-peptides and show that T_reg cells are exported from the thymus within a defined postnatal developmental window that is controlled by their increased negative selection.

Brian D. Stadinski
Sydney J. Blevins
Eric S. Huseby
Research17 Jun 2019
Nature Immunology

Volume: 20, P: 1046-1058
Hydrophobic CDR3 residues promote the development of self-reactive T cells

Through analyses of β-chain variable regions in self-reactive T cell antigen receptors, Huseby and colleagues show that an index based on the interfacial hydrophobicity of amino acids at positions 6 and 7 of the CDR3β segment distinguishes self-reactive T cell antigen receptors.

Brian D Stadinski
Karthik Shekhar
Eric S Huseby
Research27 Jun 2016
Nature Immunology

Volume: 17, P: 946-955
I-A^g7 β56/57 polymorphisms regulate non-cognate negative selection to CD4⁺ T cell orchestrators of type 1 diabetes

Type 1 diabetes is associated with homozygous expression of specific major histocompatibility complex class II beta chain polymorphisms. Here the authors show that the disease-protective effect of major histocompatibility complex class II heterozygosity is conferred by non-cognate thymocyte negative selection.

Brian D. Stadinski
Sarah B. Cleveland
Eric S. Huseby
Research20 Feb 2023
Nature Immunology

Volume: 24, P: 652-663
Prolactin induces ERα-positive and ERα-negative mammary cancer in transgenic mice

Teresa A Rose-Hellekant
Lisa M Arendt
Linda A Schuler
Research24 Jul 2003
Oncogene

Volume: 22, P: 4664-4674
Killer T cells with a beta-flavi(r) for dengue

Dysfunctional immunity is associated with dengue hemorrhagic fever and dengue shock syndrome. Structural analyses reveal that a key germline-encoded contact between the T cell antigen receptor and a peptide underpins the immunodominance of dengue-virus-specific CD8⁺ T cell responses of weak affinity.

Sydney Blevins
Eric S Huseby
News & Views18 Oct 2017
Nature Immunology

Volume: 18, P: 1186-1188
Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide

Eric S Huseby
Frances Crawford
John W Kappler
Research15 Oct 2006
Nature Immunology

Volume: 7, P: 1191-1199
Affinity for self antigen selects T_reg cells with distinct functional properties

Regulatory T cells (T_reg cells) have essential roles in maintaining immunohomeostasis. Palmer and colleagues identify two distinct subsets of T_reg cells with differing degrees of self-reactivity and regulatory function.

Lena Wyss
Brian D Stadinski
Ed Palmer
Research01 Aug 2016
Nature Immunology

Volume: 17, P: 1093-1101
αβ T cell receptors as predictors of health and disease

Meriem Attaf
Eric Huseby
Andrew K Sewell
ReviewsOpen Access26 Jan 2015
Cellular & Molecular Immunology

Volume: 12, P: 391-399

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