title: Independent CD28 signaling via VAV and SLP-76: a model for in trans costimulation.
abstract: The two-signal theory of T-cell activation dictates that optimal T-cell responses are determined by a least two signals, the primary signal provided by the antigen-receptor complex (TCR/CD3) and the second signal provided by a costimulatory receptor. Recent studies have underlined the importance of in trans costimulation via CD28 in the regulation of transplant rejection. Previous studies have emphasized the ability of CD28 to operate in cis in the amplification of signaling through the T-cell receptor (TCR). Our recent work has demonstrated that CD28 can activate the lipid kinase phosphatidylinositol 3-kinase (PI-3K) and can cooperate with adapters Vav and SLP-76 to influence the induction of interleukin (IL)-2 and IL-4 transcription in the absence of TCR ligation. CD28-PI-3K binding and CD28-VAV/SLP-76 cooperativity provide a pathway to account for in trans costimulation in T-cell immunity.
authors.affiliation: Department of Haematology, Division of Investigative Sciences, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Hammersmith Hospital, London, UK. c.rudd@ic.ac.uk
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Rudd
authors.forename: Monika
authors.initials: M
authors.lastname: Raab
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism*; D018797:Cell Cycle Proteins; D006224:Cricetinae; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D018797:Cell Cycle Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C092947:SLP-76 signal Transducing adaptor proteins; C496618:VAV1 protein, human