GlaxoSmithKline.

No abstract

We have isolated recombinant lambda clones containing intact major tuber protein (patatin) genes and flanking sequences from the commercial tetraploid variety Maris Piper. The gene is composed of seven exons and six introns, spread over 4 kb of DNA. Nuclease mapping defined the 5' end of the mRNA approximately 45 bp upstream of the initiation codon. The 5' end of the gene is preceeded by a canonical TATA box sequence. The three known patatin genes encode proteins of nearly identical Mr but very different isoelectric points. The sequence of the gene does not indicate a role for patatin as one of the globulin class of plant storage proteins.

No abstract

After allogeneic stem cell transplantation, the establishment of the donor's immune system in an antigenically distinct recipient confers a therapeutic graft-versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and protracted immune dysfunction. In the last decade, a molecular-level description of alloimmune interactions and the process of immune recovery leading to tolerance has emerged. Here, new developments in understanding alloresponses, genetic factors that modify them, and strategies to control immune reconstitution are described.In Section I, Dr. John Barrett and colleagues describe the cellular and molecular basis of the alloresponse and the mechanisms underlying the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL) effect. Increasing knowledge of leukemia-restricted antigens suggests ways to separate GVHD and GVL. T cellsThe alloresponse segregates into induction, expansion, and effector phases. In the induction phase, donor CD8 and CD4 T cells interact with peptide antigens complexed with major histocompatibility complex (MHC) class I and II molecules, respectively, on antigen-presenting cells (APCs) of the recipient. The signal given by the MHC through the T-cell receptor (TCR) and CD3, CD4, or CD8 provides the first signal for Tcell activation. A full T-cell response, leading to proliferation of effector cells, requires a second signal delivered by interaction by costimulatory molecules such as CD80 and CD86 on the APCs and CD28 on the lymphocyte surface. During the expansion phase, T cells proliferate, particularly under the influence of growth factors interleukin (IL)-2 and IL-12. The milieu in which T cells expand determines whether they assume the characteristics of T helper (Th) or T cytotoxic (Tc) type 1, or Th/Tc type 2 cells, which have distinct proor antiinflammatory functional properties, respectively.