Rearranged T lymphocyte antigen receptor genes as markers of malignant T cells

Abstract

We have recently cloned a number of canine T cell receptor (TCR) Vβ genes using degenerate oligonucleotides. From the DNA sequences of the resulting clones and the canine Vβ gene sequences in the literature, seven distinct canine TCR Vβ genes were identified. Vβ specific PCR primers were designed for each of the seven TCR Vβ genes such that under defined conditions, each primer could only amplify a specific TCR Vβ gene in conjunction with the same 3′ constant region (Cβ) primer. By performing RT-PCR on RNA derived from a source containing T lymphocytes, the presence and expansion of T cells expressing a particular Vβ gene could be detected. Moreover, the clonality or diversity of a T cell population under analysis could be easily determined by the VDJ junctional sequence of the amplified Vβ PCR product, in the form of a “DNA fingerprint”. These findings have been used to detect canine T cell lymphoma, and could potentially be used to monitor the remission of T cell malignancies in response to treatment.