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.

ABSTRACT

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) Vß-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 Vß specificity suggested that some of the SAg isoforms identified in this study have Vß 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.