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Background  Superantigens (SAgs) of mouse mammary tumor viruses (MMTVs) play a crucial role in T cell selection in the thymus in a T cell receptor (TCR) Vβ-specific manner and SAgs presented by B cells activate T cells in the periphery. The peripheral T cell repertoire is dynamically shaped by the steady induction of T cell tolerance against self antigens throughout the lifespan. We hypothesize that  de novo  somatic mutation of endogenous MMTV SAgs contributes to the modulation of the peripheral T cell repertoire.    Results  SAg coding sequences were cloned from the genomic DNAs and/or cDNAs of various tissues of female C57BL/6J mice. A total of 68 unique SAg sequences (54 translated sequences) were identified from the genomic DNAs of liver, lungs, and bone marrow, which are presumed to harbor only three endogenous MMTV loci ( Mtv-8 ,  Mtv-9 , and  Mtv-17 ). Similarly, 69 unique SAg sequences (58 translated sequences) were cloned from the cDNAs of 18 different tissues. Examination of putative TCR Vβ specificity suggested that some of the SAg isoforms identified in this study have Vβ specificities different from the reference SAgs of  Mtv-8 ,  Mtv-9 , or  Mtv-17 .    Conclusion  The pool of diverse SAg isoforms, generated by  de novo  somatic mutation, may play a role in the shaping of the peripheral T cell repertoire including the autoimmune T cell population.

bmc immunology

Prevalent de novo somatic mutations in superantigen genes of mouse mammary tumor viruses in the genome of C57BL/6J mice and its potential implication in the immune system