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The Journal of Immunology, 1999, 162: 871-877.
Copyright © 1999 by The American Association of Immunologists

Alternative Splicing and Hypermutation of a Nonproductively Rearranged TCR {alpha}-Chain in a T Cell Hybridoma1

Brendan Marshall2,*, Ruth Schulz{dagger}, Min Zhou* and Andrew Mellor*

* Institute of Molecular Medicine and Genetics, Program in Molecular Immunology, Medical College of Georgia, Augusta, GA 30912; and {dagger} Division of Molecular Immunology, National Institute for Medical Research, Mill Hill, London, United Kingdom

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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