Biology subjects

Hertz, T.

Publications and source records attributed to Hertz, T..

3 recordsLinked to original sources

bioRxiv2026

Probiotic formula intervention in infants leads to colonization and competitive strain displacement independent of IgA binding

Early-life microbiota assembly is affected by environmental exposure, diet, and immunity. We performed shotgun metagenomics sequencing of fecal samples (N=401) from a controlled infant intervention trial to evaluate how pre- and probiotic exposure affects bacterial strain dynamics, maternal-to-offspring strain transmissibility, strain persistence, and host immune responses. Species- and strain-level analyses revealed that the early-life intervention with Bifidobacterium longum subsp. infantis (BL subsp. infantis), Bifidobacterium breve, and galacto-oligosaccharides (GOS) replaced main resident strains of these species unlike breast-feeding and exclusive infant formula. BL subsp. infantis low-diversity clusters were representative of several populations and were enriched for genes linked to recombination, mobilization, and antimicrobial activity. lnterestingly, Bifidobacterium bifidum but not Bifidobacterium longum or B. breve was heavily targeted by mucosal lgA, regardless of feeding type. These findings suggest that early-life pro- and prebiotic interventions promote colonization of specific dominant strains, potentially by outcompeting and displacing existing strains, independently of host immune responses.

microbiology↗

bioRxiv2025

Computational design of HLA class I superbinders for broad T cell immunogenicity

Human leukocyte antigen (HLA) class I molecules are highly polymorphic, restricting peptide binding to narrow sequence subsets. Designing peptides that bind multiple HLA supertypes-- termed superbinders--offers a promising strategy for broad-spectrum T-cell vaccines and immunotherapies. Here we present superHLA, a computational framework that combines Markov Chain Monte Carlo optimization with state-of-the-art MHC binding predictors to design synthetic 9-mer peptides with broad HLA-binding profiles. Using superHLA, we generated over 190,000 candidate superbinders predicted to bind 8-12 HLA class I alleles across distinct supertypes. A multi-tier filtering pipeline--incorporating sequence clustering, synthesis feasibility, cross-predictor validation, and self-peptidome exclusion--yielded a final panel of 100 peptides for experimental testing. Of these, 21 bound [≥]4 supertypes in vitro, including one that bound 9. Superbinders displayed distinct anchor residue preferences and showed minimal similarity to human peptides. These results suggest that HLA superbinders are more abundant than previously recognized and can be rationally designed at scale. This approach supports development of pan-HLA immunogens with broad population coverage and potential applications in vaccine design, neoantigen discovery, and immunotherapy.

immunology↗

bioRxiv2020

TCR meta-clonotypes for biomarker discovery with tcrdist3: quantification of public, HLA-restricted TCR biomarkers of SARS-CoV-2 infection

As the mechanistic basis of adaptive cellular antigen recognition, T cell receptors (TCRs) encode clinically valuable information that reflects prior antigen exposure and potential future response. However, despite advances in deep repertoire sequencing, enormous TCR diversity complicates the use of TCR clonotypes as clinical biomarkers. We propose a new framework that leverages antigen-enriched repertoires to form meta-clonotypes - groups of biochemically similar TCRs - that can be used to robustly identify and quantify functionally similar TCRs in bulk repertoires. We apply the framework to TCR data from COVID-19 patients, generating 1831 public TCR meta-clonotypes from the 17 SARS-CoV-2 antigen-enriched repertoires with the strongest evidence of HLA-restriction. Applied to independent cohorts, meta-clonotypes targeting these specific epitopes were more frequently detected in bulk repertoires compared to exact amino acid matches, and 59.7% (1093/1831) were more abundant among COVID-19 patients that expressed the putative restricting HLA allele (FDR < 0.01), demonstrating the potential utility of meta-clonotypes as antigen-specific features for biomarker development. To enable further applications, we developed an open-source software package, tcrdist3, that implements this framework and facilitates flexible workflows for distance-based TCR repertoire analysis.

immunology↗