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- Title
CTLA-4 lacking the cytoplasmic domain costimulates IL-2 production in T-cell hybridomas.
- Authors
HUEBER, AXEL J.; MATZKIES, FRANZISKA G.; RAHMEH, MARTINA; MANGER, BERNHARD; KALDEN, JOACHIM R.; NAGEL, THOMAS
- Abstract
Optimal T-cell activation depends on the antigen-specific signal mediated by the TCR and engagement of costimulatory receptors such as CD28. CTLA-4, a homologous counterpart of CD28, is considered to be a crucial inhibitory receptor. To test its function separately from CD28 in an antigen-driven and ligand-specific model, we stably transfected the T-cell hybridomas A1.1 and DO11.10, which lack significant endogenous CD28 or CTLA-4 expression, with wild-type CTLA-4 (CTLA-4 WT) and a construct lacking the cytoplasmic tail (tailless [TL]). Functional studies were carried out by co-incubation with APC expressing the B7 ligands for CTLA-4 and appropriate MHC molecules loaded with their cognate antigens. IL-2 production on costimulation of CTLA-4WT and TCR did not differ significantly from untransfected controls. However, coligation of TCR and CTLA-4TL resulted in a vigorous IL-2 response specific for the interaction of CTLA-4 with B7. Thus, lack of the cytoplasmic tail converted CTLA-4 into a costimulatory receptor. This indicates that the CTLA-4 inhibitory function may not be attributable to sequestration of the common B7 ligands when competing with CD28. Rather, ligation of B7 by the CTLA-4 extracellular domain can enhance TCR activation, whereas in the full-length receptor, inhibitory signals mediated by the cytoplasmic domain may override this activation.
- Subjects
HYBRIDOMAS; CYTOPLASM; INTERLEUKIN-2; T cells; CD antigens; LIGANDS (Biochemistry)
- Publication
Immunology & Cell Biology, 2006, Vol 84, Issue 1, p51
- ISSN
0818-9641
- Publication type
Article
- DOI
10.1111/j.1440-1711.2005.01402.x