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Alternative splicing and hypermutation of a nonproductively rearranged TCR alpha-chain in a T cell hybridoma

Marshall, B.; Schulz, R.; Zhou, M.; Mellor, A.

Journal of Immunology 162(2): 871-877

1999

ISSN/ISBN: 0022-1767
PMID: 9916710
Document Number: 512011
Like Ig genes, TCR genes are formed by somatic rearrangements of noncontiguous genomic V, J, and C regions. Unlike Ig genes, somatic hypermutation of TCR V regions is an infrequent event. We describe the occurrence of spontaneous hypermutation in a nonproductively rearranged TCR alpha-chain gene in a clonal T cell hybridoma that had lost its productively rearranged alpha-chain. The mutating hybridoma was eventually supplanted in culture by a nonmutating variant that had restored an open reading frame in the nonproductively rearranged TCR alpha-chain through the use of cryptic splice sites in the V alpha region. Evidence is presented for the presence of cDNA reverse transcripts of the TCR alpha-chain within the hybridoma, suggesting a role for reverse transcriptase in the generation of mutations.

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