Mechanisms of T Cell Activation

TOPICAL COLLECTIONS

Guest Editors

Alexandre Carmo

University of Porto, Institute of Molecular and Cellular Biology

Alexandre Carmo graduated with a Bachelor's degree in Biochemistry at the University of Lisbon in 1987, finished an MSc in Immunology at the University of Porto in 1991, and moved to the laboratory of Alan Williams at Oxford University, where he obtained a DPhil. in Immunology in 1995. After postdocs in the laboratories of Don Mason and Maria de Sousa, he started the Cell Activation and Gene Expression group at the Institute of Molecular and Cellular Biology in 2003, moving to the Institute of Investigation and Innovation in Health, University of Porto in 2015. Research in Alex Carmo’s laboratory addresses mechanisms of T cell activation and the impact that cell surface receptors have in regulating immune and inflammatory responses. We have focused our studies on receptors belonging to the scavenger receptor cysteine-rich (SRCR) family, in particular CD5 and CD6, which are expressed by T cells. Our aim is to characterize, in depth, the molecular mechanisms underlying signaling regulation by these important receptors from their binding to extracellular ligands, transducing signals to cytosolic effectors and downstream transcription factors, and regulating the architecture of the immunological synapse. Research has been steadily moving on to study function in disease and therapy, by including other SRCR members such as the circulating proteins CD5L, SSC4D, and SSC5D. We have been performing a systematic assessment of the role of SRCR proteins in pathogen recognition and inflammation, having developed several knockout mouse models and assessed their susceptibility to infection and inflammation.

Rita F. Santos

i3s, University of Porto

Rita F. Santos graduated in Biomedical Sciences from the Polytechnic Institute of Porto in 2012 and then completed a master's degree in Molecular and Cellular Biology at the University of Aveiro. Rita developed her master's thesis in the Cell Activation and Gene Expression group at the Institute of Molecular and Cellular Biology under the supervision of Alexandre Carmo. Her main interest in investigating the features that regulate the immune response led her to pursue her studies in the field and enroll in the PhD program in Molecular and Cellular Biology at the University of Porto. During her PhD, Rita dissected the functional role of the T cell surface protein CD6 in regulating T cell activation with a special interest in the importance of this molecule during autoimmunity. Currently, Rita is a Junior Researcher in the Immune Regulation group at i3S, where she is interested in understanding the molecular pathways that drive progressive fibrosis in patients with interstitial lung diseases. Rita kept her interest in T cell biology and was granted a fellowship to characterize the T cell response in hypersensitivity pneumonitis patients’ upon fungal exposure.

Collection Overview

Gone are the days when T cell activation mechanisms and signaling pathways were inferred from stimulating T cells with phorbol esters, calcium ionophores, plant lectins, or monoclonal antibodies targeting molecules on the surface of T cells. The outputs were primarily calcium signals, protein phosphorylation, or cell proliferation.

T cells are now understood to be physiologically activated not by soluble factors but through functional encounters with antigen-presenting cells (APCs). These APCs display antigenic determinants complexed with MHC molecules on their surface, which are specifically recognized by clonotypic receptors on the T cell surface. Subsequently, signals are transduced to inner components of the cell through biochemical activation pathways.

Recent advancements have led to the development of refined methods for studying T cell activation in real-time. On the antigen-presenting side, researchers utilize genetically engineered APCs, cell-derived giant plasma membrane vesicles, supported lipid bilayers, or more conventional functionalized surfaces.T cell responses are observed in real-time using various cutting-edge microscopic techniques, including confocal, TIRF, STED, SMLM, and MINFLUX microscopies. Enzymatic activation or reaction localization can be determined through BRET or FRET analysis. Additionally, researchers can measure phenotypic changes at both the whole cell population and single-cell levels through in-depth immune-phenotyping using advanced flow or mass cytometry, as well as single-cell multi-omics approaches. These innovative techniques contribute to a more comprehensive understanding of T cell activation and signaling processes.

This Collection invites researchers who wish to see their state-of-the-art methods publicized to a vast but specialized audience to submit their methods. The goal is to help experts in T cell activation to devise the best possible strategy to couple one or multiple different technologies to address their pressing scientific and technical questions on T cell activation mechanisms.