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With unseparated mouse spleen cells as responders, Drosophila cells expressing M HC class I (L d ) molecules alone lead to peptide-specific responses of CD8 + cells in the absence of exogenous cytokines. Under these conditions, DNA released from dying cells stimulates the B cells in spleen to up-regulate costimulatory molecules; these activated B cells then provide bystander costimulation...
Thymic epithelium is involved in negative selection, but its precise role in selecting the CD4 T cell repertoire remains elusive. By using two transgenic mice, we have investigated how medullary thymic epithelium (mTE) and bone marrow (BM)-derived cells contribute to tolerance of CD4 T cells to nuclear β-galactosidase (β-gal). CD4 T cells were not tolerant when β-gal was expressed in thymic BM-derived...
Using a chemically homogeneous radiolabeled peptide of high specific activity ( 125 l-QLSPYPFDL, 3.5 x 10 18 cpm per mole) we show that at a peptide concentration (5 pM) causing half-maximal lysis of target cells by a cytolytic T lymphocyte (CTL) clone that recognizes the peptide in association with L d , a class I MHC protein, only 3 peptide molecules on average...
Somatic hypermutation in immunoglobulin variable region genes occurs within germinal centers. Here, we describe a subset of germinal center dark zone centroblasts that express only sIgD and have accumulated up to 80 mutations per heavy chain variable region (IgV H δ gene). Over half of the hypermutated IgV H δ sequences were found to be clonally related. This level of mutation is not...
T lymphocyte receptor CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with high avidity and negatively regulates T cell activation. CTLA-4 functions at the cell surface, yet is primarily localized in intracellular vesicles. Here, we demonstrate cycling of CTLA-4 between intracellular stores and the cell surface. Intracellular vesicles containing CTLA-4 overlapped with endocytic compartment(s)...
T cell antigen receptor (TCR) stimulation induces tyrosine phosphorylation of many intracellular proteins, including the proto-oncogene Vav, which is expressed exclusively in hematopoietic and trophoblast cells. Vav is critical for lymphocyte development and activation. Overexpression of Vav in Jurkat T cells leads to potentiation of TCR-mediated IL-2 gene activation. However, the biochemical function...
Cross-linking the TCR in T cell hybridomas induces cell apoptosis following activation. This activation- induced apoptosis has been used as a model for clonal deletion of thymocytes or peripheral T cells. Anti-TCR- induced apoptosis of T cell hybridomas requires de novo macromolecular synthesis, including up-regulation of Fas and FasL. The Fas-FasL interactiom then activates the apoptosis program...
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