Project Details
Projekt
Elucidating Chicken γδ T Cell Functions and Ligands via Genetically Engineered Chicken Models
Subject Area
Veterinary Medical Science
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 434524639
Gamma delta T cells play a critical role in the immune system of mammals, responding to diverse antigens, including CD1 and butyrophilin molecules. In chickens, however, the functions of gamma delta T cells and their ligands remain poorly understood. Our project aims to unravel the role of potential chicken gamma delta T cell ligands - CD1, butyrophilin, and BG molecules in immune responses to pathogens and vaccines.We hypothesize that these molecules are essential for gamma delta T cell function in chickens, either by recognizing pathogen molecules (e.g., Salmonella lipids presented by CD1) or influencing mucosal integrity (mediated by butyrophilin or BG molecules). To test this hypothesis, we will employ state-of-the-art biochemical and genetic approaches, including CRISPR/Cas9-mediated gene knockouts, to evaluate the role of these ligands in vivo. Aim 1: Investigating CD1 Molecules: We will produce CD1 multimers and assess their ability to bind gamma delta T cells. Using CRISPR/Cas9, we will generate chickens lacking CD1 genes and evaluate phenotypic changes, alterations in gamma delta T cell populations, and immune responses to key pathogens and vaccines, including MDV, IBDV, AIV, and Salmonella. Aim 2: Elucidating Butyrophilin Molecules: We will study two chicken butyrophilin genes, one located near the MHC and the other outside it. Multimers of these molecules will be tested for gamma delta T cell binding. Gene knockouts will be performed to determine the effects on receptor expression, gamma delta T cell repertoires, and immune responses to pathogens and vaccines. Aim 3: Assessing BG Molecules: We will investigate BG molecules as potential gamma delta T cell ligands by producing homo- and heterodimers and testing their interaction with gamma delta T cells. Knockouts of the BG1 gene or the entire BG locus will help assess their role in immune regulation, gamma delta T cell functionality, and vaccine-induced immunity. This study will not only shed light on the fundamental biology of chicken gamma delta T cells but also provide insights into immune responses in vertebrates. By addressing critical knowledge gaps, our research may pave the way for improved vaccine strategies and disease control in poultry.
DFG Programme
Research Units
Subproject of
FOR 5130:
ImmunoChick- Unravelling the avian immune response in the context of infection
International Connection
United Kingdom
