Antigen

About: Antigen is a research topic. Over the lifetime, 170233 publications have been published within this topic receiving 6982342 citations. The topic is also known as: antibody generator & Antigen.

Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells

Abstract: T lymphocytes expressing the T cell receptor (TCR)-γδ recognize unknown antigens on tumor cells. Here we identify metabolites of the mevalonate pathway as the tumor ligands that activate TCR-γδ cells. In tumor cells, blockade of hydroxy-methylglutaryl-CoA reductase (HMGR), the rate limiting enzyme of the mevalonate pathway, prevents both accumulation of mevalonate metabolites and recognition by TCR-γδ cells. When metabolite accumulation is induced by overexpressing HMGR or by treatment with nitrogen-containing bisphosphonate drugs, tumor cells derived from many tissues acquire the capacity to stimulate the same TCR-γδ population. Accumulation of mevalonate metabolites in tumor cells is a powerful danger signal that activates the immune response and may represent a novel target of tumor immunotherapy.

Imaging of germinal center selection events during affinity maturation.

Abstract: The germinal center (GC) is an important site for the generation and selection of B cells bearing high-affinity antibodies, yet GC cell migration and interaction dynamics have not been directly observed. Using two-photon microscopy of mouse lymph nodes, we revealed that GC B cells are highly motile and extend long cell processes. They transited between GC dark and light zones and divided in both regions, although these B cells resided for only several hours in the light zone where antigen is displayed. GC B cells formed few stable contacts with GC T cells despite frequent encounters, and T cells were seen to carry dead B cell blebs. On the basis of these observations, we propose a model in which competition for T cell help plays a more dominant role in the selection of GC B cells than previously appreciated.

The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins.

Abstract: The antigen defined by mAb Ki-67 is a human nuclear protein the expression of which is strictly associated with cell proliferation and which is widely used in routine pathology as a "proliferation marker" to measure the growth fraction of cells in human tumors. Ki-67 detects a double band with apparent molecular weights of 395 and 345 kD in immunoblots of proteins from proliferating cells. We cloned and sequenced the full length cDNA, identified two differentially spliced isoforms of mRNA with open reading frames of 9,768 and 8,688 bp encoding for this cell proliferation-associated protein with calculated molecular weights of 358,761 D and 319,508 D, respectively. New mAbs against a bacterially expressed part and a synthetic polypeptide deduced from the isolated cDNA react with the native Ki-67 antigen, thus providing a circle of evidence that we have cloned the authentic Ki-67 antigen cDNA. The central part of the Ki-67 antigen cDNA contains a large 6,845-bp exon with 16 tandemly repeated 366-bp elements, the "Ki-67 repeats", each including a highly conserved new motif of 66 bp, the "Ki-67 motif", which encodes for the epitope detected by Ki-67. Computer analysis of the nucleic acid and the deduced amino acid sequence of the Ki-67 antigen confirmed that the cDNA encodes for a nuclear and short-lived protein without any significant homology to known sequences. Ki-67 antigen-specific antisense oligonucleotides inhibit the proliferation of IM-9 cell line cells, indicating that the Ki-67 antigen may be an absolute requirement for maintaining cell proliferation. We conclude that the Ki-67 antigen defines a new category of cell cycle-associated nuclear nonhistone proteins.

T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1

Abstract: Studies using monoclonal antibodies (mAbs) have implicated the homodimeric glycoprotein CD28 as an important regulator of human T-cell activation, in part by posttranscriptional control of cytokine mRNA levels. Although the CD28 antigen has functional and structural characteristics of a receptor, a natural ligand for this molecule has not been identified. Here we show that the CD28 antigen, expressed in Chinese hamster ovary (CHO) cells, mediated specific intercellular adhesion with human lymphoblastoid and leukemic B-cell lines and with activated primary murine B cells. CD28-mediated adhesion was not dependent upon divalent cations. Several mAbs were identified that inhibited CD28-mediated adhesion, including mAb BB-1 against the B-cell activation antigen B7/BB-1 and some mAbs against major histocompatibility complex class I antigens. B7/BB-1 expression correlated closely with CD28-mediated adhesion, but class I expression did not. Transfected COS cells expressing the B7/BB-1 antigen adhered to CD28+ CHO cells; this adhesion was blocked by mAbs to CD28 and B7/BB-1. The specific recognition by CD28 of the B-cell activation antigen B7/BB-1 represents a heterophilic interaction between members of the immunoglobulin superfamily that may serve to regulate T-cell cytokine levels at sites of B-cell activation.