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© Research
Publication : Molecular immunology

Activation induced cytidine deaminase mutant (AID-His130Pro) from Hyper IgM 2 patient retained mutagenic activity on SHM artificial substrate

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular immunology - 04 Oct 2016

Ouadani H, Ben-Mustapha I, Ben-Ali M, Larguèche B, Jovanic T, Garcia S, Arcangioli B, Elloumi-Zghal H, Fathallah D, Hachicha M, Masmoudi H, Rougeon F, Barbouche MR

Link to Pubmed [PMID] – 27716525

Mol. Immunol. 2016 11;79:77-82

Activation induced cytidine deaminase (AID) is an essential enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) during secondary immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2 syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering either of the two mechanisms requires the DNA deamination activity of AID. Besides, different domains of AID may be differentially involved in CSR and SHM through their interaction with specific cofactors. Herein, we studied the AID-induced SHM activity of the AID-His130Pro mutant identified in a patient with Hyper IgM 2 syndrome. AID mutagenic activity was monitored by the reversion of nonsense mutations of the EGFP gene assessed by flow cytometry. We found that the His130Pro mutation, which affects CSR, preserves AID mutagenic activity. Indeed, the His130 residue is located in a putative specific CSR region in the APOBEC-like domain, known to involve CSR specific cofactors that probably play a major role in AID physiological activities.

https://www.ncbi.nlm.nih.gov/pubmed/27716525