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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.

Lee YK, Chiu S, Chew A, Greenhalgh DG, Cho K - BMC Immunol. (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Shriners Hospitals for Children Northern California and Department of Surgery, University of California-Davis, Sacramento, CA 95817, USA.

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) 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.

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Related in: MedlinePlus

Comparison of the hypervariable regions of MMTV SAg cDNA isoforms and their putative TCR Vβ specificity. A. Phylogenetic tree of the C-terminus hypervariable regions of 56 SAg cDNA isoforms isolated from 18 different tissues. The C-terminus hypervariable regions (~74 amino acids) of the 56 SAg cDNA isoforms were phylogenetically analyzed. The C-terminus sequences that were found in more than one tissue type are indicated using various shapes and shades: black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30); gray box and black triangle (sequences [non-reference] shared among different tissues). * indicates a representative C-terminus sequence shared among different tissues. B. Phylogenic relatedness of 17 unique C-terminus sequences selected from the 56 SAg isoforms, which were isolated from 18 different tissues. Four reference C-terminus sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30 are highlighted with gray. black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30). C. Comparison of the C-terminus hypervariable regions of 17 SAg isoforms. The unique C-terminus sequences of 17 SAg isoforms were compared with ones from four reference SAg sequences of Mtv-8, Mtv-9, Mtv-17, and Mtv-30. The SAg isoforms, identical to the individual reference SAgs, are indicated using various gray shades. D. Putative TCR Vβ specificity of SAg isoforms. Divergence of the SAg isoforms in regard to their putative TCR Vβ specificity was estimated by comparison with the TCR Vβ specificity of four reference SAg sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30.
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Figure 3: Comparison of the hypervariable regions of MMTV SAg cDNA isoforms and their putative TCR Vβ specificity. A. Phylogenetic tree of the C-terminus hypervariable regions of 56 SAg cDNA isoforms isolated from 18 different tissues. The C-terminus hypervariable regions (~74 amino acids) of the 56 SAg cDNA isoforms were phylogenetically analyzed. The C-terminus sequences that were found in more than one tissue type are indicated using various shapes and shades: black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30); gray box and black triangle (sequences [non-reference] shared among different tissues). * indicates a representative C-terminus sequence shared among different tissues. B. Phylogenic relatedness of 17 unique C-terminus sequences selected from the 56 SAg isoforms, which were isolated from 18 different tissues. Four reference C-terminus sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30 are highlighted with gray. black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30). C. Comparison of the C-terminus hypervariable regions of 17 SAg isoforms. The unique C-terminus sequences of 17 SAg isoforms were compared with ones from four reference SAg sequences of Mtv-8, Mtv-9, Mtv-17, and Mtv-30. The SAg isoforms, identical to the individual reference SAgs, are indicated using various gray shades. D. Putative TCR Vβ specificity of SAg isoforms. Divergence of the SAg isoforms in regard to their putative TCR Vβ specificity was estimated by comparison with the TCR Vβ specificity of four reference SAg sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30.

Mentions: In this study, to determine whether changes in the hypervariable C-terminus regions of the SAg isoforms, which are known to determine the TCR Vβ specificity, affect their superantigenic function, we examined the putative TCR Vβ specificity of the SAg cDNA isoforms isolated from various tissues. Initially, unique C-terminus sequences (~74 amino acids) of individual SAg cDNA isoforms were selected within each tissue, and a total of 56 sequences were identified from all 18 tissues (Figure 3A). A phylogenetic analysis of the 56 C-terminus sequences identified 17 unique hypervariable region sequences (Figure 3B). Then, the 17 SAg C-terminus sequences were subjected to alignment analyses to identify the regions responsible for determining their putative TCR Vβ specificities (Figure 3C). The matching C-terminus sequences of the Mtv-8, Mtv-9, Mtv-17, and Mtv-30 SAgs and their reported TCR Vβ specificities were used as references [5,20,29,30]. Among the 17 unique C-terminus sequences, only four of them were 100 % homologous to the Mtv-8, Mtv-9, Mtv-17, or Mtv-30 SAg (Figure 3C/D).


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.

Lee YK, Chiu S, Chew A, Greenhalgh DG, Cho K - BMC Immunol. (2011)

Comparison of the hypervariable regions of MMTV SAg cDNA isoforms and their putative TCR Vβ specificity. A. Phylogenetic tree of the C-terminus hypervariable regions of 56 SAg cDNA isoforms isolated from 18 different tissues. The C-terminus hypervariable regions (~74 amino acids) of the 56 SAg cDNA isoforms were phylogenetically analyzed. The C-terminus sequences that were found in more than one tissue type are indicated using various shapes and shades: black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30); gray box and black triangle (sequences [non-reference] shared among different tissues). * indicates a representative C-terminus sequence shared among different tissues. B. Phylogenic relatedness of 17 unique C-terminus sequences selected from the 56 SAg isoforms, which were isolated from 18 different tissues. Four reference C-terminus sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30 are highlighted with gray. black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30). C. Comparison of the C-terminus hypervariable regions of 17 SAg isoforms. The unique C-terminus sequences of 17 SAg isoforms were compared with ones from four reference SAg sequences of Mtv-8, Mtv-9, Mtv-17, and Mtv-30. The SAg isoforms, identical to the individual reference SAgs, are indicated using various gray shades. D. Putative TCR Vβ specificity of SAg isoforms. Divergence of the SAg isoforms in regard to their putative TCR Vβ specificity was estimated by comparison with the TCR Vβ specificity of four reference SAg sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 3: Comparison of the hypervariable regions of MMTV SAg cDNA isoforms and their putative TCR Vβ specificity. A. Phylogenetic tree of the C-terminus hypervariable regions of 56 SAg cDNA isoforms isolated from 18 different tissues. The C-terminus hypervariable regions (~74 amino acids) of the 56 SAg cDNA isoforms were phylogenetically analyzed. The C-terminus sequences that were found in more than one tissue type are indicated using various shapes and shades: black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30); gray box and black triangle (sequences [non-reference] shared among different tissues). * indicates a representative C-terminus sequence shared among different tissues. B. Phylogenic relatedness of 17 unique C-terminus sequences selected from the 56 SAg isoforms, which were isolated from 18 different tissues. Four reference C-terminus sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30 are highlighted with gray. black diamond (identical to Mtv-8); gray triangle (identical to Mtv-9); black circle (identical to Mtv-17); black box (identical to Mtv-30). C. Comparison of the C-terminus hypervariable regions of 17 SAg isoforms. The unique C-terminus sequences of 17 SAg isoforms were compared with ones from four reference SAg sequences of Mtv-8, Mtv-9, Mtv-17, and Mtv-30. The SAg isoforms, identical to the individual reference SAgs, are indicated using various gray shades. D. Putative TCR Vβ specificity of SAg isoforms. Divergence of the SAg isoforms in regard to their putative TCR Vβ specificity was estimated by comparison with the TCR Vβ specificity of four reference SAg sequences from Mtv-8, Mtv-9, Mtv-17, and Mtv-30.
Mentions: In this study, to determine whether changes in the hypervariable C-terminus regions of the SAg isoforms, which are known to determine the TCR Vβ specificity, affect their superantigenic function, we examined the putative TCR Vβ specificity of the SAg cDNA isoforms isolated from various tissues. Initially, unique C-terminus sequences (~74 amino acids) of individual SAg cDNA isoforms were selected within each tissue, and a total of 56 sequences were identified from all 18 tissues (Figure 3A). A phylogenetic analysis of the 56 C-terminus sequences identified 17 unique hypervariable region sequences (Figure 3B). Then, the 17 SAg C-terminus sequences were subjected to alignment analyses to identify the regions responsible for determining their putative TCR Vβ specificities (Figure 3C). The matching C-terminus sequences of the Mtv-8, Mtv-9, Mtv-17, and Mtv-30 SAgs and their reported TCR Vβ specificities were used as references [5,20,29,30]. Among the 17 unique C-terminus sequences, only four of them were 100 % homologous to the Mtv-8, Mtv-9, Mtv-17, or Mtv-30 SAg (Figure 3C/D).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Shriners Hospitals for Children Northern California and Department of Surgery, University of California-Davis, Sacramento, CA 95817, USA.

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) 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.

Show MeSH
Related in: MedlinePlus