Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]

Publication Date:
2018-01-09
Publisher:
The American Association of Immunologists (AAI)
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
Published by:
http://www.aai.org/
_version_ 1839207843191848960
autor Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
beschreibung Sarcoplasmic/endoplasmic reticulum Ca 2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a 971–990-induced disease was associated with the induction of CD4 T cell responses and the epitope preferentially binds MHC class II/IA k rather than IE k . By creating IA k /and IE k /SERCA2a 971–990 dextramers, the T cell responses were determined by flow cytometry to be Ag specific. 3) SERCA2a 971–990-sensitized T cells produce both Th1 and Th17 cytokines. 4) Animals immunized with SERCA2a 971–990 showed Ag-specific Abs with enhanced production of IgG2a and IgG2b isotypes, suggesting that SERCA2a 971–990 can potentially act as a common epitope for both T cells and B cells. 5) Finally, SERCA2a 971–990-sensitized T cells were able to transfer disease to naive recipients. Together, these data indicate that SERCA2a is a critical autoantigen in the mediation of atrial inflammation in mice and that our model may be helpful to study the inflammatory events that underlie the development of conditions such as atrial fibrillation in humans.
citation_standardnr 6134047
datenlieferant ipn_articles
feed_id 333
feed_publisher The American Association of Immunologists (AAI)
feed_publisher_url http://www.aai.org/
insertion_date 2018-01-09
journaleissn 1550-6606
journalissn 0022-1767
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association of Immunologists (AAI)
quelle Journal of Immunology
relation http://www.jimmunol.org/cgi/content/short/200/2/523?rss=1
search_space articles
shingle_author_1 Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
shingle_author_2 Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
shingle_author_3 Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
shingle_author_4 Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
shingle_catch_all_1 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
Sarcoplasmic/endoplasmic reticulum Ca 2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a 971–990-induced disease was associated with the induction of CD4 T cell responses and the epitope preferentially binds MHC class II/IA k rather than IE k . By creating IA k /and IE k /SERCA2a 971–990 dextramers, the T cell responses were determined by flow cytometry to be Ag specific. 3) SERCA2a 971–990-sensitized T cells produce both Th1 and Th17 cytokines. 4) Animals immunized with SERCA2a 971–990 showed Ag-specific Abs with enhanced production of IgG2a and IgG2b isotypes, suggesting that SERCA2a 971–990 can potentially act as a common epitope for both T cells and B cells. 5) Finally, SERCA2a 971–990-sensitized T cells were able to transfer disease to naive recipients. Together, these data indicate that SERCA2a is a critical autoantigen in the mediation of atrial inflammation in mice and that our model may be helpful to study the inflammatory events that underlie the development of conditions such as atrial fibrillation in humans.
Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_2 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
Sarcoplasmic/endoplasmic reticulum Ca 2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a 971–990-induced disease was associated with the induction of CD4 T cell responses and the epitope preferentially binds MHC class II/IA k rather than IE k . By creating IA k /and IE k /SERCA2a 971–990 dextramers, the T cell responses were determined by flow cytometry to be Ag specific. 3) SERCA2a 971–990-sensitized T cells produce both Th1 and Th17 cytokines. 4) Animals immunized with SERCA2a 971–990 showed Ag-specific Abs with enhanced production of IgG2a and IgG2b isotypes, suggesting that SERCA2a 971–990 can potentially act as a common epitope for both T cells and B cells. 5) Finally, SERCA2a 971–990-sensitized T cells were able to transfer disease to naive recipients. Together, these data indicate that SERCA2a is a critical autoantigen in the mediation of atrial inflammation in mice and that our model may be helpful to study the inflammatory events that underlie the development of conditions such as atrial fibrillation in humans.
Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_3 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
Sarcoplasmic/endoplasmic reticulum Ca 2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a 971–990-induced disease was associated with the induction of CD4 T cell responses and the epitope preferentially binds MHC class II/IA k rather than IE k . By creating IA k /and IE k /SERCA2a 971–990 dextramers, the T cell responses were determined by flow cytometry to be Ag specific. 3) SERCA2a 971–990-sensitized T cells produce both Th1 and Th17 cytokines. 4) Animals immunized with SERCA2a 971–990 showed Ag-specific Abs with enhanced production of IgG2a and IgG2b isotypes, suggesting that SERCA2a 971–990 can potentially act as a common epitope for both T cells and B cells. 5) Finally, SERCA2a 971–990-sensitized T cells were able to transfer disease to naive recipients. Together, these data indicate that SERCA2a is a critical autoantigen in the mediation of atrial inflammation in mice and that our model may be helpful to study the inflammatory events that underlie the development of conditions such as atrial fibrillation in humans.
Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_4 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
Sarcoplasmic/endoplasmic reticulum Ca 2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a 971–990-induced disease was associated with the induction of CD4 T cell responses and the epitope preferentially binds MHC class II/IA k rather than IE k . By creating IA k /and IE k /SERCA2a 971–990 dextramers, the T cell responses were determined by flow cytometry to be Ag specific. 3) SERCA2a 971–990-sensitized T cells produce both Th1 and Th17 cytokines. 4) Animals immunized with SERCA2a 971–990 showed Ag-specific Abs with enhanced production of IgG2a and IgG2b isotypes, suggesting that SERCA2a 971–990 can potentially act as a common epitope for both T cells and B cells. 5) Finally, SERCA2a 971–990-sensitized T cells were able to transfer disease to naive recipients. Together, these data indicate that SERCA2a is a critical autoantigen in the mediation of atrial inflammation in mice and that our model may be helpful to study the inflammatory events that underlie the development of conditions such as atrial fibrillation in humans.
Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Khalilzad-Sharghi, V., Zhou, Y., Riethoven, J.-J., Nandi, S. S., Mishra, P. K., Sobel, R. A., Strande, J. L., Steffen, D., Reddy, J.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_title_1 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
shingle_title_2 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
shingle_title_3 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
shingle_title_4 Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
timestamp 2025-07-31T23:41:21.578Z
titel Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
titel_suche Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice [AUTOIMMUNITY]
topic WW-YZ
uid ipn_articles_6134047