Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.

Subclasses of simian virus 40 large T antigen in simian virus 40-transformed and -infected cells separated by zone velocity sedimentation in sucrose density gradients have been characterized. Three forms of large T antigen were distinguished: a 5 to 6S form, a 14 to 16S form, and a 23 to 25S form. These forms appeared to differ biochemically and biologically. Differential labeling experiments suggested that the 5 to 6S form was less highly phosphorylated than the faster-sedimenting forms. The 23 to 25S form which was complexed with one or more host phosphoproteins, as reported recently (D. P. Lane and L. V. Crawford Nature [London] 268:261-263, 1979; F. McCormick and E. Harlow, J. Virol. 34: 213-224, 1980), was prominent in extracts of transformed cells, but was also detected in productively infected cells. Pulse-chase experiments suggested that the 5 to 6S large T antigen is a precursor of the more stable, faster-sedimenting forms of T antigen. Monkey cells infected with a tsA mutant of simian virus 40 at 41 degrees C contained only 5 to 6S large T antigen, implying that this form is not active in the initiation of simian virus 40 DNA replication. In pulse-chase, shift-down experiments, DNA replication resumed, and the 5 to 6S large T antigen which had accumulated at 41 degrees C was partially converted at 33 degrees C to a fast-sedimenting form. However, shift-up experiments demonstrated that the fast-sedimenting large T antigen, once formed, remained stable at 41 degrees C, although it was unable to function in initiation. These experiments suggest that different biological functions of large T antigen may be carried out by different subclasses of this protein.

Three remarkable and unique features of the immune system are specificity, diversity, and memory. Immunological memory involves both T and B cells and results in a secondary antibody response that is faster, of higher affinity, and results in the secretion of non-IgM isotypes of Ig. In this review we discuss the properties of memory T and B cells, their specific receptors, and the events which occur both in the nucleus and on the cell surface during generation and activation of these cells. Although memory T and B cells use different mechanisms to elaborate memory, there are a number of interesting analogies: lymphokines vs antibodies and affinity maturation of B cell antigen receptors vs upregulation of adhesion molecules on T cells. Finally, we discuss the importance of these cells in health and disease and suggest what impact additional information about these cells might have on the manipulation of the immune response.

Background: 17E6, a primate-specific mouse mAb that inhibits ␣V integrins, is in phase II trials for treating cancer. Results: We determined crystal structure of the ␣V␤3-17E6 Fab complex, revealing the molecular basis of 17E6 specificity and function. Conclusion: 17E6 is an allosteric inhibitor of fibronectin-integrin interaction. Significance: The defined 17E6 epitope may help in developing novel therapeutics targeting related regions in other integrins.

The comparative analysis of Ig class switch recombination in a priori IgG/IgA-expressing myelomas and hybridomas, in switch variants and in activated normal B cells shows the following characteristics of class switch recombination in activated B cells: It is prevented during most of B cell ontogeny. It happens on both IgH loci of activated and switched B cells. The recombination is programmed in that on both IgH loci of switched cells the same switch regions recombine with Smu. This is true at least for the IgG1 pathway. IgM-expressing cells show no class switch recombination on the inactive IgH locus. Thus, physiological class switch recombination is a programmed rather than a random event and is controlled as such. The initial stages of class switching and the molecules involved in these are largely unclear: What is the nature of the protection of switch regions and how is this protection abrogated? Do specific recombinases exist? What is the role of large transcription units? Is the specificity of class switch recombination a result of specific "opening" of the DNA for transcription? Do all B cells use the same switch mechanism? What is the role of switch factors (such as lymphokines)? These and more questions await answers and although a variety of switch scenarios could be discussed at present a detailed speculation seems premature.