Structural basis of specificity and cross-reactivity in T cell receptors specific for cytochrome c-I-E(k).

T cells specific for the cytochrome c Ag are widely used to investigate many aspects of TCR specificity and interactions with peptide-MHC, but structural information has long been elusive. In this study, we present structures for the well-studied 2B4 TCR, as well as a naturally occurring variant of the 5c.c7 TCR, 226, which is cross-reactive with more than half of possible substitutions at all three TCR-sensitive residues on the peptide Ag.

Regulation of insulin-responsive aminopeptidase expression and targeting in the insulin-responsive vesicle compartment of glucose transporter isoform 4-deficient cardiomyocytes.

In adipocytes and cardiac or skeletal muscle, glucose transporter isoform 4 (GLUT4) is targeted to insulin-responsive intracellular membrane vesicles (IRVs) that contain several membrane proteins, including insulin-responsive aminopeptidase (IRAP) that completely colocalizes with GLUT4 in basal and insulin-treated cells. Cardiac GLUT4 content is reduced by 65-85% in IRAP knockout mice, suggesting that IRAP may regulate the targeting or degradation of GLUT4. To determine whether GLUT4 is required for maintenance of IRAP content within IRVs, we studied the expression and cellular localization of IRAP and other GLUT4 vesicle-associated proteins, in hearts of mice with cardiac-specific deletion of GLUT4 (G4H-/-).

Uncompromised generation of a specific H-2DM-dependent peptide-MHC class II complex from exogenous antigen in Leishmania mexicana-infected dendritic cells.

Leishmania infection inhibits the capacity of macrophages (MPhi) to present antigens to CD4(+) T cells. Relocation of MHC class II and H-2DM to the parasitophorous vacuole (PV) and their subsequent degradation by the parasite may contribute to this defect. Dendritic cells (DC) are critical for initiation of primary T cell responses.

Rapid constitutive generation of a specific peptide-MHC class II complex from intact exogenous protein in immature murine dendritic cells.

MHC class II molecules present peptides, derived largely from exogenous antigens, to CD4+ T cells. Complex-generation occurs mainly in the specialized late endosomal MHC class II-rich compartment (MIIC) vesicles of antigen-presenting cells (APC). Dendritic cells (DC) have been reported to store intact antigen in MIIC until the receipt of an activation signal, when they process it into peptide-MHC class II complexes.

Dendritic cells: immunological features and utilisation for tumour immunotherapy.

The prospect of developing 'magic bullets' to attack tumour cells has been a goal of biologists for decades. Abundant experimental and clinical observations demonstrating that an effective specific immune response may engender tumour regression has prompted efforts to find an immunotherapeutic approach to this problem. The most important arm of cellular immunity for such responses appears to be cytotoxic T-lymphocytes (CTL) which can recognise antigen on virtually all cell types and which are key to the elimination of virally-infected cells.