A new study provides important insights into how T-cells, a type of immune cell, become activated. Researchers employed a technique called Bayesian metamodeling, which combines data from different sources, including advanced microscopy and simulations, to analyze the activation process more effectively. This research accounts for a surprising pattern in how immune cells communicate and signal to one another. Understanding this pattern could deepen our knowledge of cellular behavior and the mechanisms behind immune responses, potentially leading to improved treatments for various diseases.
A new study at the Hebrew University of Jerusalem, led by Yair Neve-Oz from the Racah Institute of Physics and School of Computer Science and Engineering, Dr. Barak Raveh from the School of Computer Science and Engineering, and Eilon Sherman from the Racah Institute of Physics, has made an important breakthrough in understanding how immune cells known as T cells are activated. By using an innovative approach called Bayesian metamodeling, the team combined data from advanced super-resolution microscopy techniques and stochastic computer simulations to reveal new, intricate patterns in early T-cell signaling.
T cells are key players in the immune system, responding specifically and efficiently to threats. Specifically, T cells act as sensitive agents that can identify the presence of infected or cancerous cells, and efficiently clear them. However, until now, existing microscopic models have only partially captured the molecular processes behind early T-cell activation, leaving gaps in our understanding. The Hebrew University team’s metamodel brings these models together, drawing from data on how critical molecules—T-cell receptors (TCR), CD45, and Lck—interact and move at the initial points of contact between T cells and target cells.
A key discovery in a previous study from the Sherman lab (https://doi.org/10.1016/j.celrep.2019.11.022) is a nanoscale ring of activated TCR molecules, surprisingly appearing around the edge of initial T cell contacts and framed by a ring of CD45 molecules. This pattern could not be explained by current models of T cell activation. The researchers suggest that this pattern arises because Lck molecules, which help transmit signals between TCR and CD45, are restricted in their activity range. This limitation plays a crucial role in how TCRs get activated during the early immune response.
The team also analyzed how variations in Lck activity, specific antigen strengths, and forms of CD45 impact T-cell activation. These findings offer a more complete view of early T-cell signaling, with potential applications in understanding other complex cellular processes. Bayesian metamodeling, by integrating different models into a cohesive whole, offers a powerful tool for uncovering the hidden patterns that drive cellular behavior, with broad implications for immunology and medical research.
This study represents a significant advance in immunology, shedding light on the intricate cellular dynamics that underpin our immune responses.
The research paper titled “Bayesian metamodeling of early T-cell antigen receptor signaling accounts for its nanoscale activation patterns” is now available in Frontiers in Immunology and can be accessed HERE.