Abstract 7267: Development and validation of a novel humanized B-hTRBC1/hTRBC2 mouse model for T cell activation

Abstract The gene encoding the TCR constant β chain (TRBC) has two isoforms: TRBC1 and TRBC2. Each TCR (and therefore each T cell) irreversibly selects a TCR β-chain constant region encoded by either TRBC1 or TRBC2 for expression in a mutually exclusive manner. Normal T cells consist of both TRBC1 and TRBC2; however, malignant T cells contain only one of the two isoforms. In the treatment of TRBC1+ or TRBC2+ T cell malignancies, selectively targeting TRBC1 or TRBC2, respectively, can effectively eliminate the malignant clone without significantly compromising the integrity of the T cell compartment, thereby preventing severe immunosuppression. This study introduces a novel B-hTRBC1/hTRBC2 mouse model for the investigation of T cell activation and includes an extensive analysis of its phenotypic and immunological characteristics. Gene and protein expression of human TRBC1/TRBC2 in these mice were confirmed using RT-PCR and flow cytometry, respectively. The study also found comparable development, differentiation, and distribution of immune cells in the spleen, blood, and lymph nodes between B-hTRBC1/hTRBC2 mice and wild-type C57BL/6 mice. Notably, normal T cell proliferation and cytokine production were observed in vitro in response to anti-mCD3E and anti-hTRBC1 antibody treatments, demonstrating the functionality of humanized T cells in these mice. In summary, our data indicate that B-hTRBC1/hTRBC2 mice provide a powerful preclinical model for in vivo/ex vivo evaluation of T cell activation. Citation Format: Hannah Horton, Zhixia Li, Shufeng Wang, Zhenlan Niu, Lei Zhao, Yanling Wang, Xiaofei Zhou. Development and validation of a novel humanized B-hTRBC1/hTRBC2 mouse model for T cell activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7267.