A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity

The anti-La mab 312B, which was established by hybridoma technology from human-La transgenic mice after adoptive transfer of anti-human La T cells, immunoprecipitates both native eukaryotic human and murine La protein. Therefore, it represents a true anti-La autoantibody. During maturation, the anti...

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Autores principales:	Tabea Bartsch, Claudia Arndt, Liliana R. Loureiro, Alexandra Kegler, Edinson Puentes-Cala, Javier Andrés Soto, Biji T. Kurien, Anja Feldmann, Nicole Berndt, Michael P. Bachmann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	anti-La/SS-B antibodies autoimmunity La/SS-B autoantigen systemic lupus erythematosus primary Sjögren’s syndrome Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/81bdb80441084ae9a22ff72a15acbb10
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spelling	oai:doaj.org-article:81bdb80441084ae9a22ff72a15acbb102021-11-11T17:26:32ZA Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity10.3390/ijms2221120461422-00671661-6596https://doaj.org/article/81bdb80441084ae9a22ff72a15acbb102021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12046https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The anti-La mab 312B, which was established by hybridoma technology from human-La transgenic mice after adoptive transfer of anti-human La T cells, immunoprecipitates both native eukaryotic human and murine La protein. Therefore, it represents a true anti-La autoantibody. During maturation, the anti-La mab 312B acquired somatic hypermutations (SHMs) which resulted in the replacement of four aa in the complementarity determining regions (CDR) and seven aa in the framework regions. The recombinant derivative of the anti-La mab 312B in which all the SHMs were corrected to the germline sequence failed to recognize the La antigen. We therefore wanted to learn which SHM(s) is (are) responsible for anti-La autoreactivity. Humanization of the 312B ab by grafting its CDR regions to a human Ig backbone confirms that the CDR sequences are mainly responsible for anti-La autoreactivity. Finally, we identified that a single amino acid replacement (D > Y) in the germline sequence of the CDR3 region of the heavy chain of the anti-La mab 312B is sufficient for anti-La autoreactivity.Tabea BartschClaudia ArndtLiliana R. LoureiroAlexandra KeglerEdinson Puentes-CalaJavier Andrés SotoBiji T. KurienAnja FeldmannNicole BerndtMichael P. BachmannMDPI AGarticleanti-La/SS-B antibodiesautoimmunityLa/SS-B autoantigensystemic lupus erythematosusprimary Sjögren’s syndromeBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12046, p 12046 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-La/SS-B antibodies autoimmunity La/SS-B autoantigen systemic lupus erythematosus primary Sjögren’s syndrome Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	anti-La/SS-B antibodies autoimmunity La/SS-B autoantigen systemic lupus erythematosus primary Sjögren’s syndrome Biology (General) QH301-705.5 Chemistry QD1-999 Tabea Bartsch Claudia Arndt Liliana R. Loureiro Alexandra Kegler Edinson Puentes-Cala Javier Andrés Soto Biji T. Kurien Anja Feldmann Nicole Berndt Michael P. Bachmann A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity
description	The anti-La mab 312B, which was established by hybridoma technology from human-La transgenic mice after adoptive transfer of anti-human La T cells, immunoprecipitates both native eukaryotic human and murine La protein. Therefore, it represents a true anti-La autoantibody. During maturation, the anti-La mab 312B acquired somatic hypermutations (SHMs) which resulted in the replacement of four aa in the complementarity determining regions (CDR) and seven aa in the framework regions. The recombinant derivative of the anti-La mab 312B in which all the SHMs were corrected to the germline sequence failed to recognize the La antigen. We therefore wanted to learn which SHM(s) is (are) responsible for anti-La autoreactivity. Humanization of the 312B ab by grafting its CDR regions to a human Ig backbone confirms that the CDR sequences are mainly responsible for anti-La autoreactivity. Finally, we identified that a single amino acid replacement (D > Y) in the germline sequence of the CDR3 region of the heavy chain of the anti-La mab 312B is sufficient for anti-La autoreactivity.
format	article
author	Tabea Bartsch Claudia Arndt Liliana R. Loureiro Alexandra Kegler Edinson Puentes-Cala Javier Andrés Soto Biji T. Kurien Anja Feldmann Nicole Berndt Michael P. Bachmann
author_facet	Tabea Bartsch Claudia Arndt Liliana R. Loureiro Alexandra Kegler Edinson Puentes-Cala Javier Andrés Soto Biji T. Kurien Anja Feldmann Nicole Berndt Michael P. Bachmann
author_sort	Tabea Bartsch
title	A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity
title_short	A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity
title_full	A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity
title_fullStr	A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity
title_full_unstemmed	A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity
title_sort	small step, a giant leap: somatic hypermutation of a single amino acid leads to anti-la autoreactivity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/81bdb80441084ae9a22ff72a15acbb10
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A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity

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