The genome of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), the infectious agent etiologically associated with the acquired immunodeficiency syndrome, contains, in addition to the genes for the polymerase, core, and envelope proteins, several open reading frames. To investigate whether the 3' open reading frame (3' orf) located between the envelope gene and the 3' long terminal repeat is a gene expressed in vivo in infected individuals, we inserted a fragment of 3' orf in a prokaryotic expression vector. The protein product synthesized in bacteria was purified and allowed to react with sera from individuals infected with human T-cell lymphotropic virus type III as indicated by seropositivity for other viral proteins. Two-thirds of the sera, regardless of the clinical status of the individuals, reacted with the purified protein indicating that 3' orf is a viral gene the product of which is immunogenic in vivo. A polyclonal rabbit antiserum reacting against the 3' orf gene product was obtained by serial injection of rabbits with the purified bacterial protein. The antiserum recognized a 27-kDa protein in the human T-cell lymphotropic virus type III-infected lymphocytes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC323935 | PMC |
http://dx.doi.org/10.1073/pnas.83.14.5282 | DOI Listing |
Mol Ther Methods Clin Dev
March 2025
Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
T cell-based immunotherapies targeting antigens on tumor cells have shown efficacy as anti-cancer treatments. While neoantigens are created by somatic mutations acquired during tumorigenesis, allogeneic stem cell transplantation as treatment for hematological malignancies exploits minor histocompatibility antigens encoded by genetic differences between patients and donors. Screening methods to predict neoantigens and minor histocompatibility antigens typically consider only conventional antigens created by nonsynonymous mutations or polymorphisms coding for amino acid changes in canonical open reading frames (ORFs).
View Article and Find Full Text PDFiScience
January 2025
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Bristol Myers Squibb Research & Development, 700 Bay Road, Redwood City, California 94063, United States.
Dual activation of the TLR7 and TLR8 pathways leads to the production of type I interferon and proinflammatory cytokines, resulting in efficient antigen presentation by dendritic cells to promote T-cell priming and antitumor immunity. We developed a novel series of TLR7/8 dual agonists with varying ratios of TLR7 and TLR8 activity for use as payloads for an antibody-drug conjugate approach. The agonist-induced production of several cytokines in human whole blood confirmed their functional activity.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Biomedical Research Institute of Southern California, Oceanside, CA, United States.
Interferon types-I/II (IFN-αβ/γ) secretions are well-established antiviral host defenses. The human immunodeficiency virus (HIV) particles are known to prevail following targeted cellular interferon secretion. CD4 T-lymphocytes are the primary receptor targets for HIV entry, but the virus has been observed to hide (be latent) successfully in these cells through an alternate entry route via interactions with LFA1.
View Article and Find Full Text PDFResearch (Wash D C)
January 2025
Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
Immune recognition and activation by the peptide-laden major histocompatibility complex-T cell receptor (TCR)-CD3 complex is essential for anti-tumor immunity. Tumors may escape immune surveillance by dissembling the complex. Here, we report that transferrin, which is overexpressed in patients with liver metastasis, disassociates TCR from the CD3 signaling apparatus by targeting the constant domain (CD) of T cell receptor α (TCRα), consequently suppresses T cell activation, and inhibits anti-metastatic and anti-tumor immunity.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!