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Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI.
bioRxiv
November 2024
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown.
View Article and Find Full Text PDFThe mouse monoclonal antibody 4E3 is specific for the G1m17 allotype of human IgG1.
J Immunol Methods
November 2024
Thermo Fisher Scientific, Uppsala, Sweden.
Allotype is an amino acid variation within the immunoglobulin isotypes. Four allotypes have been described for human IgG1 and two of them (G1m3 and G1m17) are located at position 214 in the CH1 region of the gamma chain. Various diseases have been associated with allotype expression, making the allotype research an interesting field in immunology.
View Article and Find Full Text PDFIdentification and structural characterization of a mutant KRAS-G12V specific TCR restricted by HLA-A3.
Eur J Immunol
September 2024
Division of Intramural Research (DIR), Laboratory of Immunogenetics, NIAID, NIH, Bethesda, Maryland, USA.
Mutations in KRAS are some of the most common across multiple cancer types and are thus attractive targets for therapy. Recent studies demonstrated that mutant KRAS generates immunogenic neoantigens that are targetable by adoptive T-cell therapy in metastatic diseases. To expand mutant KRAS-specific immunotherapies, it is critical to identify additional HLA-I allotypes that can present KRAS neoantigens and their cognate T-cell receptors (TCR).
View Article and Find Full Text PDFBreast Milk-Derived Antibodies Impair Vaccine Immunity in Suckling Mice.
J Immunol
September 2024
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Breast milk confers multiple benefits to the neonate, including passive immunity against multiple microorganisms via Abs. However, it remains unclear whether breast milk-derived Abs affect vaccine-induced immunity in the neonate. We evaluated in C57BL/6 and BALB/c mice whether breastfeeding from an mRNA-SARS-CoV-2-vaccinated dam affects vaccine-induced immunity in neonate mice.
View Article and Find Full Text PDFTargeting of intracellular oncoproteins with peptide-centric CARs.
Nature
November 2023
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks.
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