Correlation between the Amino Acid Position of Arginine in VH-CDR3 and Specificity for Native DNA among Autoimmune Antibodies

Meera R. Krishnan, Nainn Tsyr Jou, Tony Marion

Research output: Contribution to journalArticle

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Abstract

Autoimmunity to DNA in mouse models for the systemic autoimmune disease systemic lupus erythematosus (SLE) has all of the characteristics of an Ag-driven secondary immune response to DNA. Since the pathogenesis of anti-DNA Ab in SLE is correlated to Ab specificity for native DNA (dsDNA), understanding how such specificity is generated is important. As with immune Ab responses to most Ags, autoimmune Ab responses to DNA are dependent upon the clonal selection of B cells expressing particular H and L chain V-region structures. The VH structures of most autoimmune anti-DNA Abs include at least one arginine in VH-CDR3; moreover, previous results led us to propose that anti-DNA Ab specificity for dsDNA may be dependent upon the relative position of arginines in VH-CDR3. The present results demonstrate a strong correlation between specificity for dsDNA and arginine position in VH-CDR3, for Abs with VH encoded by VH genes from the VH7183, VH Q52, and VH S107 families but not from the VH558 family. Specificity for dsDNA was not only correlated to the presence of VH-CDR3 arginines but also to the relative position of the arginines in VH-CDR3. The majority of the VH-CDR3 arginines appeared to have been encoded by sequences generated during V-D-J recombination. These results are not only important for understanding how Ab specificity for dsDNA is generated but also how somatically derived structures generated during V-D-J recombination may influence clonotype selection of an immune response within an individual mouse.

Original languageEnglish (US)
Pages (from-to)2430-2439
Number of pages10
JournalJournal of Immunology
Volume157
Issue number6
StatePublished - Sep 15 1996

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Arginine
Amino Acids
Antibodies
V(D)J Recombination
Autoimmunity
Systemic Lupus Erythematosus
Autoimmune Diseases
B-Lymphocytes
Genes

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Correlation between the Amino Acid Position of Arginine in VH-CDR3 and Specificity for Native DNA among Autoimmune Antibodies. / Krishnan, Meera R.; Jou, Nainn Tsyr; Marion, Tony.

In: Journal of Immunology, Vol. 157, No. 6, 15.09.1996, p. 2430-2439.

Research output: Contribution to journalArticle

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abstract = "Autoimmunity to DNA in mouse models for the systemic autoimmune disease systemic lupus erythematosus (SLE) has all of the characteristics of an Ag-driven secondary immune response to DNA. Since the pathogenesis of anti-DNA Ab in SLE is correlated to Ab specificity for native DNA (dsDNA), understanding how such specificity is generated is important. As with immune Ab responses to most Ags, autoimmune Ab responses to DNA are dependent upon the clonal selection of B cells expressing particular H and L chain V-region structures. The VH structures of most autoimmune anti-DNA Abs include at least one arginine in VH-CDR3; moreover, previous results led us to propose that anti-DNA Ab specificity for dsDNA may be dependent upon the relative position of arginines in VH-CDR3. The present results demonstrate a strong correlation between specificity for dsDNA and arginine position in VH-CDR3, for Abs with VH encoded by VH genes from the VH7183, VH Q52, and VH S107 families but not from the VH558 family. Specificity for dsDNA was not only correlated to the presence of VH-CDR3 arginines but also to the relative position of the arginines in VH-CDR3. The majority of the VH-CDR3 arginines appeared to have been encoded by sequences generated during V-D-J recombination. These results are not only important for understanding how Ab specificity for dsDNA is generated but also how somatically derived structures generated during V-D-J recombination may influence clonotype selection of an immune response within an individual mouse.",
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