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Interleukin-1
Published in Jason Kelley, Cytokines of the Lung, 2022
Timothy R. Aksamit, Gary W. Hunninghake
One of the most important effects of IL-1 may be a generalized activation of the immune system in response to host injury. In this capacity, it interacts with other cytokines. The largest potential source of IL-1 is monocytes/macrophages. A primary function of IL-1 is to activate lymphocytes. T cells usually require two signals for activation (Weiss et al., 1984; Truneh et al., 1985). The first signal is proper presentation of an antigen by an antigen-presenting cell, such as the macrophage. This antigen binds to a specific T-cell receptor. The second signal usually involves binding of IL-1 to the T-cell IL-1 receptor (Mizel, 1982). Subsequent studies have shown, however, that IL-1–induced T-cell activation may not be completely explained by this two-signal model (Abraham et al., 1987). After activation, the T cell begins to divide and increases production of both IL-2 and the IL-2 receptor (Mizel, 1982; Arya and Gallo, 1984; Raulet, 1985). Release of IL-2 augments the release of other cytokines (Dinarello and Mier, 1987; Herrmann et al., 1988; Munoz et al., 1990). Synergistic effects between IL-1 and IL-6 have been observed for activation of T cells (Sironi et al., 1989; Elias et al., 1989; Helle et al., 1989).
The Inducible System: Antigens
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The T cell receptor recognizes fragments of protein antigens which are nestled in a surface groove on the MHC protein on the membrane of an antigen-presenting cell. These peptides are created in the cytoplasm of the antigen-presenting cell by protein-digesting organelles called proteosomes. The peptides bound to class I MHC proteins are eight to ten amino acids in length and approximately thirteen amino acids in length for those bound to class II MHC proteins. These sequences are too short to have any secondary or tertiary structure. The TCR is specific for both the conformation of the MHC protein and the primary structure of the antigen fragment. Because of this characteristic of the T cell receptor, cell mediated immunity is limited to responses to sequential antigenic sites. B cell receptors and the humoral immune response, on the other hand, may be induced by both sequential and conformational epitopes.
Acquired Immunity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Several interactions between antigen and T-cell receptor must take place for T-cell activation. The antigen must be presented to the T cell as a peptide fragment within a groove of the MHC molecules on the APCs. The T cell receptor only recognizes the foreign protein together with self MHC. The combination of TCR, MHC molecule and antigen fragment (peptide) is known as trimolecular complex.
Generation of a novel fully human non-superagonistic anti-CD28 antibody with efficient and safe T-cell co-stimulation properties
Published in mAbs, 2023
Abdullah Elsayed, Christian Pellegrino, Louis Plüss, Frederik Peissert, Ramon Benz, Franziska Ulrich, Gudrun Thorhallsdottir, Sheila Dakhel Plaza, Alessandra Villa, Jacqueline Mock, Emanuele Puca, Roberto De Luca, Markus G. Manz, Cornelia Halin, Dario Neri
Cytotoxic T cells are key mediators of the adaptive immune system to fight cancer. The discovery of the T-cell receptor (TCR) revealed the mechanism of how T cells become activated upon antigen recognition.1–3 TCR engagement is initiated by recognizing antigenic peptides, such as tumor antigens, presented by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs) and tumor cells.4,5 TCRs lack an intracellular signaling domain. Therefore, their association with CD3 and other co-receptors (e.g., CD4, CD8) is necessary to trigger an activation signal cascade, referred to as “signal 1.”6–9 However, signal 1 alone is typically insufficient for the full activation of T cells. The absence of an additional signal induces T-cell anergy and impairs T-cell activity.10,11 The CD28 receptor provides a crucial costimulatory signal that enhances T-cell proliferation, survival, and production of key cytokines (e.g., IL-2); this costimulatory effect is referred to as “signal 2.”12–15 CD28 is a homo-dimeric glycoprotein that is constitutively expressed on the surface membrane of most T cells (around 95% of CD4+ and 50% of CD8+ T cells).16 In the immune synapse, CD28 binds to its counter receptors, CD80 and CD86, primarily expressed on APCs.17–21
Expression and clinical significance of RAG1 in myelodysplastic syndromes
Published in Hematology, 2022
Xiaoke Huang, Xiaolin Liang, Shanhu Zhu, Qiongni Xie, Yibin Yao, Zeyan Shi, Zhenfang Liu
The plasticity of the acquired immune system in recognizing millions of possible antigens is largely due to the combinatorial joining of variable (V), diversity (D), and joining (J) gene segments that encode the antigen-binding regions of T cell receptors (TCRs) in T cells and B cell receptors (BCRs) in B cells, and the junctional diversity that can be introduced during the process of V(D)J recombination[5]. RAG1 and RAG2 proteins form a complex and initiate V(D)J recombination by introducing DNA double-strand breaks (DSBs) between the recombination signal sequences and the flanking V, D, or J gene segment. The human RAG1 protein consists of 1,043 amino acids, and the catalytic core (amino acids 387–1011) contains a nonamer-binding domain, a dimerization and DNA binding domain, a pre-RNase H and catalytic RNase H domain, 2 zinc-binding domains, and the carboxy-terminal domain, which are all crucial for V(D)J recombination[6, 7].
Circulating biomarkers of response to immunotherapy and immune-related adverse events
Published in Expert Review of Molecular Diagnostics, 2022
Zachary Garrison, Noah Hornick, Jeffrey Cheng, Rajan P. Kulkarni
T-cell receptor (TCR) repertoire is a term used to encompass the diversity of the TCR population found on surfaces of an individual’s T-cells and the corresponding antigen specificity. TCR repertoires are often very diverse within tumor cell populations. These receptors, which have an unmatched role in driving immune response, dictate the variety of signals and markers that can elicit a targeted response. As such, TCR repertoire is a useful framework for analyzing and classifying immune cell preparedness. Typical analysis of TCR repertoire requires sequencing of the desired immune cells via bulk or single-cell TCR sequencing. While both approaches can provide information, single-cell analysis is required to analyze useful chain pairing trends [46]. Recent evidence has shown that thymus cell states can heavily influence TCR repertoire throughout the lifespan of an individual [47]. With such a crucial role within the overall framework of immunity, it is not surprising to find that TCR repertoire has been linked to influences in immune therapy response.