In birds and mammals T cells develop along two discrete pathways characterized by expression of either the alpha beta or the gamma delta T-cell antigen receptors (TCRs). To gain further insight into the evolutionary significance of the gamma delta T-cell lineage, the present studies sought to define the chicken TCR gamma locus. A splenic cDNA library was screened with two polymerase chain reaction products obtained from genomic DNA using primers for highly conserved regions of TCR and immunoglobulin genes. This strategy yielded cDNA clones with characteristics of mammalian TCR gamma chains, including canonical residues considered important for proper folding and stability. Northern blot analysis with the TCR gamma cDNA probe revealed 1.9-kb transcripts in the thymus, spleen, and a gamma delta T-cell line, but not in B or alpha beta T-cell lines. Three multimember V gamma subfamilies, three J gamma gene segments, and a single constant region C gamma gene were identified in the avian TCR gamma locus. Members of each of the three V gamma subfamilies were found to undergo rearrangement in parallel during the first wave of thymocyte development. TCR gamma repertoire diversification was initiated on embryonic day 10 by an apparently random pattern of V-J gamma recombination, nuclease activity, and P-and N-nucleotide additions to generate a diverse repertoire of avian TCR gamma genes early in ontogeny.
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http://dx.doi.org/10.1073/pnas.93.26.15329 | DOI Listing |
Int J Mol Sci
January 2025
Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain.
Class IA PI3K p110δ and p110α subunits participate in TCR and costimulatory receptor signals involved in T cell-mediated immunity, but the role of p110α is not completely understood. Here, we analyzed a mouse model of the Cre-dependent functional inactivation of p110α (kinase dead) in T lymphocytes (p110αKD-T, KD). KD mice showed increased cellularity in thymus and spleen and altered T cell differentiation with increased number of CD4CD8 DP thymocytes, enhanced proportion of CD4 SP lymphocytes linked to altered apoptosis, lower Treg cells, and increased AKT and ERK phosphorylation in activated thymocytes.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Medigene Immunotherapies GmbH, 82152 Planegg-Martinsried, Germany.
Background/objectives: MDG1011 is an autologous TCR-T therapy developed as a treatment option for patients with myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). It is specific for the target antigen PReferentially expressed Antigen in MElanoma (PRAME). The recombinant TCR used in MDG1011 recognizes PRAME VLD-peptide presented by HLA-A*02:01-encoded surface molecules.
View Article and Find Full Text PDFFront Immunol
January 2025
Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM, United States.
Squamate reptiles are amongst the most successful terrestrial vertebrate lineages, with over 10,000 species across a broad range of ecosystems. Despite their success, squamates are also amongst the least studied lineages immunologically. Recently, a universal lack of γδ T cells in squamates due to deletions of the genes encoding the T cell receptor (TCR) γ and δ chains was discovered.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Hepatobiliary Pancreatic Surgery.
T cells targeting a KRAS mutation can induce durable tumor regression in some patients with metastatic epithelial cancer. It is unknown whether T cells targeting mutant KRAS that are capable of killing tumor cells can be identified from peripheral blood of patients with pancreatic cancer. We developed an in vitro stimulation approach and identified HLA-A*11:01-restricted KRAS G12V-reactive CD8+ T cells and HLA-DRB1*15:01-restricted KRAS G12V-reactive CD4+ T cells from peripheral blood of 2 out of 6 HLA-A*11:01-positive patients with pancreatic cancer whose tumors expressed KRAS G12V.
View Article and Find Full Text PDFMethods Cell Biol
January 2025
Institute of Immunology, Christian-Albrechts University and University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany. Electronic address:
T cells expressing the γδ T-cell receptor (TCR) represent a numerically small proportion of total T cells. Unlike αβ T cells they are activated by non-peptide antigens independently of MHC-presentation. γδ T cells have been recognized as a favorable prognostic marker across different tumor entities.
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