The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the therapeutic efficacy of T11F, D5A, the derivative most active in vitro, and F11A, characterized by a different conformation, was investigated in larvae infected with . A single injection of F11A and D5A derivatives, in contrast with T11F, led to a significant increase in survival of larvae injected with a lethal inoculum of cells, in comparison with infected animals treated with saline. Peptide modulation of host immunity upon infection was determined by hemocyte analysis and larval histology, highlighting a different immune stimulation by the studied peptides. F11A, particularly, was the most active in eliciting nodule formation, melanization and fat body activation, leading to a better control of yeast infection. Overall, the obtained data suggest a double role for F11A, able to simultaneously target the fungus and the host immune system, resulting in a more efficient pathogen clearance.
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http://dx.doi.org/10.3390/ijms222010904 | DOI Listing |
Cells
December 2024
Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA.
Chronic stress, a risk factor for many neuropsychiatric conditions, causes dysregulation in the immune system in both humans and animal models. Additionally, inflammation and synapse loss have been associated with deficits in social behavior. The complement system, a key player of innate immunity, has been linked to social behavior impairments caused by chronic stress.
View Article and Find Full Text PDFJ Transl Med
November 2024
Navy Medical University, Shanghai, 200433, China.
Over the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a revolutionary immunotherapeutic approach to combat cancer. This therapy constructs a CAR on the surface of T cells through genetic engineering techniques. The CAR is formed from a combination of antibody-derived or ligand-derived domains and T-cell receptor (TCR) domains.
View Article and Find Full Text PDFNat Biomed Eng
December 2024
Westlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Chimeric antigen receptor (CAR) T cells targeting receptors on tumour cells have had limited success in patients with glioblastoma. Here we report the development and therapeutic performance of CAR constructs leveraging protein binders computationally designed de novo to have high affinity for the epidermal growth factor receptor (EGFR) or the tumour-associated antigen CD276, which are overexpressed in glioblastoma. With respect to T cells with a CAR using an antibody-derived single-chain variable fragment as antigen-binding domain, the designed binders on CAR T cells promoted the proliferation of the cells, the secretion of cytotoxic cytokines and their resistance to cell exhaustion, and improved antitumour performance in vitro and in vivo.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2024
Department of Chemistry, University of California-Berkeley, Berkeley, CA 94720.
Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells. While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell signal integration mechanisms that rely on monovalent, membrane-associated, and relatively weakly binding ligand in the context of cellular adhesion. Commonly used antibodies and their derivatives bind much more strongly than native peptide major histocompatibility complex (pMHC) ligands bind their cognate TCRs.
View Article and Find Full Text PDFmBio
October 2024
Virology Division, USA Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, USA.
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