A5013833418- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Yersinia bacterium, plague, ectoparasites research
- Cardiovascular Issues in Pregnancy
- Viral Infections and Vectors
- Immune responses and vaccinations
- Kawasaki Disease and Coronary Complications
- Zoonotic diseases and public health
- Vasculitis and related conditions
- Viral gastroenteritis research and epidemiology
University of Oxford
2020-2025
Oxfam
2020
Pathogen-specific CD8 + T cell responses restricted by the nonpolymorphic nonclassical class Ib molecule human leukocyte antigen E (HLA-E) are rarely reported in viral infections. The natural HLA-E ligand is a signal peptide derived from classical Ia HLA molecules that interact with NKG2/CD94 receptors to regulate killer functions, but pathogen-derived peptides can also be presented HLA-E. Here, we describe five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited...
Abstract The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 regulate NK cell-mediated cytotoxicity. Here we report isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing HLA-E-VL9-expressing cells by an NKG2A + line. Structural analysis reveal 3H4 acts preventing CD94/NKG2A docking on HLA-E-VL9....
MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. can also present sequence-diverse, lower-affinity, pathogen-derived T cell receptors (TCRs) on CD8+ cells. To understand these affinity differences, human (HLA-E)-VL9 versus peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and parameters. In...
Summary Mutations in KRAS are some of the most common across multiple cancer types and thus attractive targets for therapy. Recent studies demonstrated that mutant generates immunogenic neoantigens can be targeted adoptive T cell therapy metastatic diseases. To expand specific immunotherapies, it is critical to identify additional HLA-I allotypes present their cognate receptors (TCR). Here, we identified a murine TCR KRAS-G12V neoantigen ( 7 VVVGAVGVGK 16 ) using vaccination approach with...
Abstract Natural killer (NK) cells kill target following triggering via germline-encoded receptors interacting with cell-expressed ligands (direct killing), or antibody-dependent cellular cytotoxicity (ADCC) mediated by FcγRIIIa. NK is modulated signaling through activating inhibitory receptors. A major checkpoint the receptor NKG2A/CD94 and its cell ligand, HLA-E, which complexed HLA signal sequence-derived peptides termed VL9 (HLA-E-VL9). We have previously reported isolation of a murine...
Abstract Mutations in KRAS are some of the most common across multiple cancer types and thus attractive targets for therapy. Recent studies demonstrated that mutant generates immunogenic neoantigens targetable by adoptive T‐cell therapy metastatic diseases. To expand KRAS‐specific immunotherapies, it is critical to identify additional HLA‐I allotypes can present their cognate receptors (TCR). Here, we identified a murine TCR specific KRAS‐G12V neoantigen ( 7 VVVGA V GVGK 16 ) using...
ABSTRACT HLA-E is a non-classical class Ib molecule that has limited polymorphism and binds HLA Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 regulate NK cell-mediated cytotoxicity. Here we isolated murine IgM antibody 3H4, specifically recognized bound enhanced killing of HLA-E-VL9-expressing cells by an NKG2A + line. Structural analysis revealed how 3H4 prevents CD94/NKG2A docking on binding overlapping footprint. Upon in...