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

B Marshall1, R Schulz, M Zhou

  • 1Institute of Molecular Medicine and Genetics, Program in Molecular Immunology, Medical College of Georgia, Augusta 30912-3175, USA. marshall@immag.mcg.edu

Journal of Immunology (Baltimore, Md. : 1950)
|January 23, 1999
PubMed

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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