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 forin vivo/ex vivoevaluation of T cell activation.