{'fraction_non_alphanumeric': 0.0348122866894198, 'fraction_numerical': 0.023890784982935155, 'mean_word_length': 5.573991031390134, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
CTLA‐4 lacking the cytoplasmic domain costimulates IL‐2 production in T‐cell hybridomas

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.