Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response

Micah T. McClain, Carol Lutz, Kenneth M. Kaufman, Ofer Z. Faig, Timothy F. Gross, Judith A. James

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Abstract

A subset of lupus patients with severe nephritis and anti-nRNP reactivity produces autoantibodies primarily against two major epitopes of the nRNP A (also known as U1A) protein. These sequences span amino acids 44-56 (A3) and amino acids 103-115 (A6). These two epitopes represent structurally different regions of the protein, as both epitopes are located on the surface, but the A6 epitope is functionally masked in vivo by binding between nRNP A and the U1 RNA. Rabbits were immunized with either the A3 or A6 peptides constructed on a branching polylysine backbone. Rabbits immunized with each of these peptides first developed antibodies directed against the peptide of immunization. With boosting, the immune response of rabbits immunized with the A3 peptide spread to other common antigenic regions of nRNP A. These regions of nRNP A bound by A3 immunized rabbits are very similar to common epitopes in human systemic lupus erythematosus. These A3 immunized rabbits also develop antibodies to common antigenic regions of nRNP 70K, nRNP C, Sm B/B′, and Sm D1 proteins, as well as clinical symptoms of systemic lupus erythematosus such as leukopenia and renal insufficiency. On the other hand, rabbits immunized with the A6 peptide only develop antibodies to the peptide of immunization. Anti-A3, but not anti-A6, antibodies are capable of immunoprecipitating native small nuclear ribonucleoprotein complexes. Immunization with the A3 peptide of nRNP A (a surface epitope), but not the A6 peptide (masked), induces an extensive, varied immune response against multiple small nuclear ribonucleoprotein autoantigens similar to that seen in human systemic lupus erythematosus.

Original languageEnglish (US)
Pages (from-to)3551-3556
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number10
DOIs
StatePublished - Mar 9 2004

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Autoimmunity
Epitopes
Rabbits
Peptides
Systemic Lupus Erythematosus
Small Nuclear Ribonucleoproteins
Immunization
Antibodies
Polylysine
Nephritis
Leukopenia
Autoantibodies
Renal Insufficiency
Anti-Idiotypic Antibodies
Amino Acid Sequence
Proteins
Amino Acids
acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response",
abstract = "A subset of lupus patients with severe nephritis and anti-nRNP reactivity produces autoantibodies primarily against two major epitopes of the nRNP A (also known as U1A) protein. These sequences span amino acids 44-56 (A3) and amino acids 103-115 (A6). These two epitopes represent structurally different regions of the protein, as both epitopes are located on the surface, but the A6 epitope is functionally masked in vivo by binding between nRNP A and the U1 RNA. Rabbits were immunized with either the A3 or A6 peptides constructed on a branching polylysine backbone. Rabbits immunized with each of these peptides first developed antibodies directed against the peptide of immunization. With boosting, the immune response of rabbits immunized with the A3 peptide spread to other common antigenic regions of nRNP A. These regions of nRNP A bound by A3 immunized rabbits are very similar to common epitopes in human systemic lupus erythematosus. These A3 immunized rabbits also develop antibodies to common antigenic regions of nRNP 70K, nRNP C, Sm B/B′, and Sm D1 proteins, as well as clinical symptoms of systemic lupus erythematosus such as leukopenia and renal insufficiency. On the other hand, rabbits immunized with the A6 peptide only develop antibodies to the peptide of immunization. Anti-A3, but not anti-A6, antibodies are capable of immunoprecipitating native small nuclear ribonucleoprotein complexes. Immunization with the A3 peptide of nRNP A (a surface epitope), but not the A6 peptide (masked), induces an extensive, varied immune response against multiple small nuclear ribonucleoprotein autoantigens similar to that seen in human systemic lupus erythematosus.",
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Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response. / McClain, Micah T.; Lutz, Carol; Kaufman, Kenneth M.; Faig, Ofer Z.; Gross, Timothy F.; James, Judith A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 10, 09.03.2004, p. 3551-3556.

Research output: Contribution to journalArticle

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T1 - Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response

AU - McClain, Micah T.

AU - Lutz, Carol

AU - Kaufman, Kenneth M.

AU - Faig, Ofer Z.

AU - Gross, Timothy F.

AU - James, Judith A.

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