Protease shaving of facilitates vaccine antigen discovery and delivery of novel cargoes to the Mtb surface.

Tuberculosis (TB) is the leading cause of infectious disease death and lacks a vaccine capable of protecting adults from pulmonary TB. The bacterial surface is a critical interface that shapes host-pathogen interactions. Several knowledge gaps persist in our understanding of (Mtb)-host interactions that may be addressed by an improved understanding of the Mtb surface proteome, including the identification of novel vaccine targets as well as developing new approaches to interrogate host-pathogen interactions.

Validation and quantification of peptide antigens presented on MHCs using SureQuant.

Vaccines and immunotherapies that target peptide-major histocompatibility complexes (peptide-MHCs) have the potential to address multiple unmet medical needs in cancer and infectious disease. Designing vaccines and immunotherapies to target peptide-MHCs requires accurate identification of target peptides in infected or cancerous cells or tissue, and may require absolute or relative quantification to identify abundant targets and measure changes in presentation under different treatment conditions. Internal standard parallel reaction monitoring (also known as 'SureQuant') can be used to validate and/or quantify MHC peptides previously identified by using untargeted methods such as data-dependent acquisition.

PathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification.

Vaccine-elicited T cell responses can contribute to immune protection against emerging infectious disease risks such as antimicrobials-resistant (AMR) microbial pathogens and viruses with pandemic potential, but rapidly identifying appropriate targets for T cell priming vaccines remains challenging. Mass spectrometry (MS) analysis of peptides presented on major histocompatibility complexes (MHCs) can identify potential targets for protective T cell responses in a proteome-wide manner. However, pathogen-derived peptides are outnumbered by self peptides in the MHC repertoire and may be missed in untargeted MS analyses.

Protease shaving of facilitates vaccine antigen discovery and delivery of novel cargoes to the Mtb surface.

Tuberculosis (TB), caused by (Mtb), is the leading cause of infectious disease death and lacks a vaccine capable of protecting adults from pulmonary TB. Studies have shown that Mtb uses a variety of mechanisms to evade host immunity. Secreted Mtb proteins such as Type VII secretion system substrates have been characterized for their ability to modulate anti-Mtb immunity; however, studies of other pathogens such as Typhi and have revealed that outer membrane proteins can also interact with the innate and adaptive immune system.

Immunopeptidomics reveals determinants of antigen presentation on MHC class I.

CD8+ T cell recognition of ()-specific peptides presented on major histocompatibility complex class I (MHC-I) contributes to immunity to tuberculosis (TB), but the principles that govern presentation of antigens on MHC-I are incompletely understood. In this study, mass spectrometry (MS) analysis of the MHC-I repertoire of -infected primary human macrophages reveals that substrates of 's type VII secretion systems (T7SS) are overrepresented among -derived peptides presented on MHC-I. Quantitative, targeted MS shows that ESX-1 activity is required for presentation of peptides derived from both ESX-1 substrates and ESX-5 substrates on MHC-I, consistent with a model in which proteins secreted by multiple T7SSs access a cytosolic antigen processing pathway via ESX-1-mediated phagosome permeabilization.

MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas.

Combining multiple therapeutic strategies in NRAS/BRAF mutant melanoma-namely MEK/BRAF kinase inhibitors, immune checkpoint inhibitors (ICIs), and targeted immunotherapies-may offer an improved survival benefit by overcoming limitations associated with any individual therapy. Still, optimal combination, order, and timing of administration remains under investigation. Here, we measure how MEK inhibition (MEKi) alters anti-tumor immunity by utilizing quantitative immunopeptidomics to profile changes in the peptide major histocompatibility molecules (pMHC) repertoire.

Leveraging Immunopeptidomics To Study and Combat Infectious Disease.

T cells must recognize pathogen-derived peptides bound to major histocompatibility complexes (MHCs) in order to initiate a cell-mediated immune response against an infection, or to support the development of high-affinity antibody responses. Identifying antigens presented on MHCs by infected cells and professional antigen-presenting cells (APCs) during infection may therefore provide a route toward developing new vaccines. Peptides bound to MHCs can be identified at whole-proteome scale using mass spectrometry-a technique referred to as "immunopeptidomics.

Structured silicon for revealing transient and integrated signal transductions in microbial systems.

Bacterial response to transient physical stress is critical to their homeostasis and survival in the dynamic natural environment. Because of the lack of biophysical tools capable of delivering precise and localized physical perturbations to a bacterial community, the underlying mechanism of microbial signal transduction has remained unexplored. Here, we developed multiscale and structured silicon (Si) materials as nongenetic optical transducers capable of modulating the activities of both single bacterial cells and biofilms at high spatiotemporal resolution.

Entropic constraints on the steady-state fitness of competing self-replicators.

Recent developments in nonequilibrium statistical mechanics suggest that the history of entropy production in a system determines the relative likelihood of competing processes. This presents the possibility of interpreting and predicting the self-organization of complex active systems, but existing theories rely on quantities that are challenging to obtain. Here, we address this issue for a general class of Markovian systems in which two types of self-replicating molecular assemblies (self-replicators) compete for a pool of limiting resource molecules within a nonequilibrium steady state.