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

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.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.Endogenous retroviruses (ERVs) are known to make up approximately 10 % of the mouse genome [1]. The available data suggest that the majority of the ERV population in the genome of C57BL/6J harbor sequences similar to murine leukemia viruses (MLVs). Limited copies of endogenous mouse mammary tumor viruses (MMTVs) are identified in the genome of almost all laboratory mouse strains, including C57BL/6J with three genomic loci of Mtv-8, Mtv-9, and Mtv-17 [2-4]. Although only three loci of endogenous MMTVs (Mtv-8, Mtv-9, and Mtv-17) are confirmed in the National Center for Biotechnology Information (NCBI) database, identification of the Mtv-30 superantigen (SAg) sequence from C57BL/6J mice has been reported [5]. Certain endogenous MMTVs, such as Mtv-2, are known to be capable of producing infectious virus particles, predominantly in the mammary gland, which are transmitted to the pups through the milk [6-9].Both endogenous and exogenous MMTVs encode SAgs from an open reading frame residing on the 3' long terminal repeat (LTR) [10,11]. MMTV SAgs, which are type II membrane proteins presented in a major histocompatibility complex class II restricted manner, are capable