Alternative splicing of murine T-cell receptor β-chain transcripts

Abstract

Variable processing of heteronuclear RNA into multiple, defined species of messenger RNA is a well-established phenomenon in a number of systems, including myelin basic protein^1,2, calcitonin³, troponin T⁴ and immunoglobulins^5–7. Within a single B cell, immunoglobulin heavy-chain peptides often exist as two related but distinct species, a membrane-bound form and a secreted form, both of which originate from the same germline constant(C)-region gene via alternative RNA processing pathways⁵. Furthermore, at certain stages of B-cell development, a single variable(V)-region element can be concurrently expressed in immunoglobulins of both the IgM and IgD isotypes, presumably resulting from the alternative splicing of one variable-region exon to different constant-region genes^6,7. We report here the existence of an alternative RNA splicing pathway available to murine T-cell receptor (TCR) β-chain transcripts. Sequence analysis of β-chain complementary DNA clones reveals a C_β 1 species containing a 72-base pair (bp) insertion between the joining (J_β) and C_β elements. This sequence is inserted via an alternative splicing pathway available to C_β1 transcripts. The optional exon is located between the J_β1 cluster and the first exon of C_β 1. Interestingly, this element can be spliced to C_β2 in the New Zealand White mouse, in which the C_β1 gene is deleted^8,9. Use of the alternative splicing pathway varies between 1% and 18% of total C_β clones, depending on the source of isolation.