Pitfalls in Bone Marrow Edema Interpretation on Dual-Energy CT: Challenges and Solutions.

Bone marrow edema (BME) is a significant imaging finding in musculoskeletal and emergency radiology, often associated with trauma or nontraumatic etiologies such as inflammation, infection, or neoplasms. Magnetic resonance imaging (MRI) remains the gold standard for BME evaluation. However, dual-energy CT (DECT) has emerged as a valuable alternative due to its faster acquisition times, lower costs, and more rapid access in emergency settings (when compared with MRI), facilitating timely decision-making when MRI is impractical or contraindicated.

Occlusion of TCR binding to HLA-A*11:01 by a non-pathogenic human alloantibody.

Over the last decades, organ transplantation has made rapid progress as a curative therapy for organ failure. However, the adaptive immune system-alloreactive T cells and antibodies targeting human leukocyte antigens (HLA)-is the leading cause of graft rejection. The presence of anti-donor HLA antibodies is considered a risk factor that disqualifies a particular donor-recipient pair.

Antigen-antibody complex density and antibody-induced HLA protein unfolding influence Fc-mediated antibody effector function.

Donor-specific antibodies (DSAs) targeting mismatched human leukocyte antigen (HLA) molecules are one of the principal threats to long-term graft survival in solid organ transplantation. However, many patients with long-term circulating DSAs do not manifest rejection responses, suggesting a degree of heterogeneity in their pathogenicity and related functional activity. Immunologic risk stratification of transplant recipients is complicated by challenges intrinsic to defining alloantibody responses that are potentially pathogenic versus those that are not.

Hybrid structural modeling of alloantibody binding to human leukocyte antigen with rapid and reproducible cross-linking mass spectrometry.

Alloantibody recognition of donor human leukocyte antigen (HLA) is associated with poor clinical transplantation outcomes. However, the molecular and structural basis for the alloantibody-HLA interaction is not well understood. Here, we used a hybrid structural modeling approach on a previously studied alloantibody-HLA interacting pair with inputs from ab initio, in silico, and in vitro data.

Themis controls T cell activation, effector functions, and metabolism of peripheral CD8 T cells.

Themis is important in regulating positive selection of thymocytes during T cell development, but its role in peripheral T cells is less understood. Here, we investigated T cell activation and its sequelae using a tamoxifen-mediated, acute Themis deletion mouse model. We find that proliferation, effector functions including anti-tumor killing, and up-regulation of energy metabolism are severely compromised.

CD28-CAR-T cell activation through FYN kinase signaling rather than LCK enhances therapeutic performance.

Signal transduction induced by chimeric antigen receptors (CARs) is generally believed to rely on the activity of the SRC family kinase (SFK) LCK, as is the case with T cell receptor (TCR) signaling. Here, we show that CAR signaling occurs in the absence of LCK. This LCK-independent signaling requires the related SFK FYN and a CD28 intracellular domain within the CAR.

Lymphoepithelial carcinoma of the larynx: an extremely rare tumour in a patient of Chinese descent.

Lymphoepithelial carcinoma (LEC) of the larynx is an extremely rare tumour which, unlike its nasopharyngeal counterpart, has shown a propensity to affect elderly Caucasian men and is not commonly associated with Epstein-Barr virus. We present a 70-year-old Chinese man who complained of hoarseness and dysphagia. Nasoendoscopy revealed a left supraglottic tumour.

Expansion of an Unusual Virtual Memory CD8 Subpopulation Bearing Vα3.2 TCR in Themis-Deficient Mice.

Deletion of the gene for Themis affects T cell selection in the thymus, which would be expected to affect the TCR repertoire. We found an increased proportion of cells expressing Vα3.2 (TRAV9N-3) in the peripheral CD8 T cell population in mice with germline deficiency.

Targeting CAR to the Peptide-MHC Complex Reveals Distinct Signaling Compared to That of TCR in a Jurkat T Cell Model.

Chimeric antigen receptor T cells (CAR-T) utilize T cell receptor (TCR) signaling cascades and the recognition functions of antibodies. This allows T cells, normally restricted by the major histocompatibility complex (MHC), to be redirected to target cells by their surface antigens, such as tumor associated antigens (TAAs). CAR-T technology has achieved significant successes in treatment of certain cancers, primarily liquid cancers.

Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.

Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.

Nonstimulatory peptide-MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling.

Foreign antigens are presented by antigen-presenting cells in the presence of abundant endogenous peptides that are nonstimulatory to the T cell. In mouse T cells, endogenous, nonstimulatory peptides have been shown to enhance responses to specific peptide antigens, a phenomenon termed coagonism. However, whether coagonism also occurs in human T cells is unclear, and the molecular mechanism of coagonism is still under debate since CD4 and CD8 coagonism requires different interactions.

Design and validation of conditional ligands for HLA-B*08:01, HLA-B*15:01, HLA-B*35:01, and HLA-B*44:05.

We designed conditional ligands restricted to HLA-B*08:01, -B*35:01, and -B*44:05 and proved the use of a conditional ligand previously designed for HLA-B*15:02 together with HLA-B*15:01. Furthermore, we compared the detection capabilities of specific HLA-B*15:01-restricted T cells using the HLA-B*15:01 and HLA-B*15:02 major histocompatibility complex (MHC) multimers and found remarkable differences in the staining patterns detected by flow cytometry. These new conditional ligands greatly add to the application of MHC-based technologies in the analyses of T-cell recognition as they represent frequently expressed HLA-B molecules.

Bioorthogonal cleavage and exchange of major histocompatibility complex ligands by employing azobenzene-containing peptides.

Bioorthogonal cleavable linkers are attractive building blocks for compounds that can be manipulated to study biological and cellular processes. Sodium dithionite sensitive azobenzene-containing (Abc) peptides were applied for the temporary stabilization of recombinant MHC complexes, which can then be employed to generate libraries of MHC tetramers after exchange with a novel epitope. This technology represents an important tool for high-throughput studies of disease-specific T cell responses.