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. 2020 Aug 24;130(10):5127–5141. doi: 10.1172/JCI137723

Figure 7. TCRs specific for the CBFB-MYH11/B*40:01 epitope confer antileukemic activity.

Figure 7

(A) Expression of transgenic TCRs in CD8+ T cells transduced (TD) with D1.C6 B1A1, D2.C8 B1A1, D2.C24 B1A1, and D3.C5 B1A2 TCR constructs or mock-TD is shown by staining with CBFB-MYH11/B*40:01 tetramer from a single experiment. (B) HLA-B*40:01+ LCLs pulsed with REEMEVHEL peptide at various concentrations were lysed in CRA by D2.C24 TCR-TD CD8+ T cells (dashed line) and D2.C24 parental clone (solid line). Mean and SEM for 3 technical replicates are shown. (C) Degranulation of D2.C24 TCR-TD CD8+ T cells and D2.C24 parental clone in response to primary AML was determined by measurement of T cell CD107a presentation in response to stimulation with primary AML (blue bars, CBFB-MYH11+ HLA-B*40:01+, n = 3 different primary AML samples; orange bars, CBFB-MYH11+ HLA-B*40:01–, n = 3; green bars, CBFB-MYH11– HLA-B*40:01+, n = 4). (D) Lysis of primary AML by D2.C24 TCR-TD CD8+ T cells, D2.C24 parental clone, and mock-TD CD8+ T cells was evaluated in a standard 4-hour CRA with E:T of 20:1 (CBFB-MYH11+ HLA-B*40:01+, n = 3 different AML samples; CBFB-MYH11+ HLA-B*40:01–, n = 6; CBFB-MYH11– HLA-B*40:01+, n = 5). For C and D, mean and SD are shown. Statistics were calculated using unpaired 2-tailed t tests with Welch’s correction.