| Autor: |
HUEBER, AXEL J., MATZKIES, FRANZISKA G., RAHMEH, MARTINA, MANGER, BERNHARD, KALDEN, JOACHIM R., NAGEL, THOMAS |
| Předmět: |
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| Zdroj: |
Immunology & Cell Biology; Feb2006, Vol. 84 Issue 1, p51-58, 8p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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