Biology subjects

Takehara, K. K.

Publications and source records attributed to Takehara, K. K..

3 recordsLinked to original sources

bioRxiv2026

The CD8 immgenT framework as a universal reference of mouse CD8 Tαβ cell differentiation states

Mouse CD8+ T cell differentiation has been studied extensively in models of infections and tumors, yet no unified framework spans the full spectrum of immunological contexts. Within the immgenT project, we profiled RNA, surface markers, and TCR clonotypes in conventional CD8+ T cells across >600 samples, spanning multiple perturbations, tissues, and timepoints. Twenty-one clusters across naive, effector, circulating memory, tissue-resident memory, progenitor-exhausted, and terminally-exhausted CD8+ T cell compartments emerged, with striking molecular convergence across acute and chronic infections, tumors, autoimmunity, aging, and homeostasis, illustrating that shared transcriptional states support protective or dysfunctional outcomes depending on developmental history and microenvironment. We validate immgenT as a comprehensive reference by integrating external datasets from conditions not represented in immgenT and by defining a flow cytometry panel spanning the CD8+ T cell landscape. Thus, immgenT-CD8 provides a molecular framework for harmonizing CD8+ T cell literature and clarifies relationships across diverse immune challenges.

immunology↗

bioRxiv2024

Monoclonal antibodies derived from B cells in subjects with cystic fibrosis reduce Pseudomonas aeruginosa burden in mice

Pseudomonas aeruginosa (PA) is an opportunistic, frequently multidrug-resistant pathogen that can cause severe infections in hospitalized patients. Antibodies against the PA virulence factor, PcrV, protect from death and disease in a variety of animal models. However, clinical trials of PcrV-binding antibody-based products have thus far failed to demonstrate benefit. Prior candidates were derivations of antibodies identified using protein-immunized animal systems and required extensive engineering to optimize binding and/or reduce immunogenicity. Of note, PA infections are common in people with cystic fibrosis (pwCF), who are generally believed to mount normal adaptive immune responses. Here we utilized a tetramer reagent to detect and isolate PcrV-specific B cells in pwCF and, via single-cell sorting and paired-chain sequencing, identified the B cell receptor (BCR) variable region sequences that confer PcrV-specificity. We derived multiple high affinity anti-PcrV monoclonal antibodies (mAbs) from PcrV-specific B cells across 3 donors, including mAbs that exhibit potent anti-PA activity in a murine pneumonia model. This robust strategy for mAb discovery expands what is known about PA-specific B cells in pwCF and yields novel mAbs with potential for future clinical use.

immunology↗

bioRxiv2019

The Development of Optimally Responsive Plasmodium-specific CD73+CD80+ IgM+ Memory B cells Requires Intrinsic BCL6 expression butnot CD4+ Tfh cells

Humoral immunity depends upon long-lived, antibody-secreting plasma cells and memory B cells (MBCs). MBCs exhibit significant phenotypic and functional heterogeneity shaped by interactions with CD4+ T cells. It is currently unclear how specific CD4+ T cell interactions with B cells influence specific MBC subset generation. We used genetic ablation and antibody depletion to dissect key CD4+ T cell/B cell receptor-ligand pair interactions to define the critical signals that govern the development of specific MBC populations. While it has previously been suggested that germinal center (GC) experience is required for the development of CD73+CD80+ MBCs that rapidly form secondary plasmablasts, highly functional IgM+ MBCs differentiate in a BCL6 and CD4+ T cell-dependent, but GC-independent manner. BCL6 upregulation, in the presence or absence of a GC, can therefore serve as a predictor of long-lived, functional MBCs. One Sentence SummaryDifferential requirements of BCL6 and Tfh cells lead to the generation of functionally distinct memory B cell populations.

immunology↗