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.
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.


CONCLUSIONS
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.
Shriners Hospitals for Children Northern California and Department of Surgery, University of California-Davis, Sacramento, CA 95817, USA.
Young-Kwan
YK
Lee
Sophia
S
Chiu
Alex
A
Chew
David G
DG
Greenhalgh
Kiho
K
Cho
D000818:Animals; D001483:Base Sequence; D033481:Chromosomes, Mammalian / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D016678:Genome / Q000235:genetics*; D007107:Immune System / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018089:Superantigens / Q000235:genetics*
D018076:DNA, Complementary; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens
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