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

Like Ig genes, TCR genes are formed by somatic rearrangements of noncontigu ous genomic V, J, and C regions. Unlike Ig genes, somatic hypermutation of TCR V regions is an infrequent event. We describe the occurrence of spontan eous hypermutation in a nonproductively rearranged TCR alpha-chain gene in a clonal T cell hybridoma that had lost its productively rearranged alpha-c hain, The mutating hybridoma was eventually supplanted in culture by a nonm utating variant that had restored an open reading frame in the nonproductiv ely rearranged TCR alpha-chain through the use of cryptic splice sites in t he V alpha region. Evidence is presented for the presence of cDNA reverse t ranscripts of the TCR alpha-chain within the hybridoma, suggesting a role f or reverse transcriptase in the generation of mutations.