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A Small Step, a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Nov 07; Vol. 22 (21). Date of Electronic Publication: 2021 Nov 07. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Amino Acids genetics
Amino Acids metabolism
Antibodies, Antinuclear immunology
Antibodies, Antinuclear metabolism
Autoantibodies chemistry
Autoantibodies immunology
Autoantibodies metabolism
Autoimmunity genetics
Complementarity Determining Regions genetics
Complementarity Determining Regions immunology
Complementarity Determining Regions metabolism
Epitopes genetics
Epitopes immunology
HeLa Cells
Humans
Recombinant Proteins genetics
Recombinant Proteins immunology
Recombinant Proteins metabolism
Sequence Analysis, Protein
Antibodies, Antinuclear genetics
Autoantibodies genetics
Somatic Hypermutation, Immunoglobulin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34769474
- Full Text :
- https://doi.org/10.3390/ijms222112046