Epistasis Between HLA-DRB1*16:02:01 and SLC16A11 T-C-G-T-T Reduces Odds for Type 2 Diabetes in Southwest American Indians.

We sought to identify genetic/immunologic contributors of type 2 diabetes (T2D) in an indigenous American community by genotyping all study participants for both high-resolution HLA-DRB1 alleles and SLC16A11 to test their risk and/or protection for T2D. These genes were selected based on independent reports that HLA-DRB1*16:02:01 is protective for T2D and that SLC16A11 associates with T2D in individuals with BMI <35 kg/m2. Here, we test the interaction of the two loci with a more complete data set and perform a BMI sensitivity test.

From antigens to immune responses: Shaping the future of TB detection and prevention.

Objectives: Tuberculosis (TB) remains a global health challenge due to various factors, including delayed diagnoses leading to the spread of infection, limited efficacy of current vaccination strategies, and emergence of drug-resistant strains. Here, we explore the significance of Mycobacterium tuberculosis (Mtb)-specific antigens to overcome these challenges.

Methods: A narrative review exploring the dynamics of Mtb-specific antigens and the related T cell immune responses across the TB spectrum.

Antigen-specificity measurements are the key to understanding T cell responses.

Antigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes. T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens.

assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors.

Gamma-delta (γδ) T cells contribute to the pathology of many immune-related diseases; however, no assays to study their activities are currently available. Here, we established a methodology to characterize human allergen-reactive γδ T cells in peripheral blood using an activation-induced marker assay targeting upregulated 4-1BB and CD69 expression. Broad and reproducible allergen-reactive γδ T cell responses were detected in donors sensitized to mouse, cockroach, house dust mite, and timothy grass, but the response did not differ from that in non-allergic participants.

Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies.

Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells to refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce "CAR Pooling," a multiplexed approach to rapidly identify CAR designs with clinical potential. Forty CARs with signaling domains derived from a range of immune cell lineages were evaluated in pooled assays for their ability to stimulate critical T cell effector functions during repetitive stimulation that mimics long-term tumor antigen exposure.

Specific gene repression by CRISPRi system transferred through bacterial conjugation.

In microbial communities, bacterial populations are commonly controlled using indiscriminate, broad range antibiotics. There are few ways to target specific strains effectively without disrupting the entire microbiome and local environment. Here, we use conjugation, a natural DNA horizontal transfer process among bacterial species, to deliver an engineered CRISPR interference (CRISPRi) system for targeting specific genes in recipient Escherichia coli cells.