Cross-reactivity and sequence similarity between microbial transglutaminase and human tissue antigens

Abstract

Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additive to glue processed nutrients. As a result, new immunogenic epitopes are generated that might drive autoimmunity. Presently, its contribution to autoimmunity through epitope similarity and cross-reactivity was investigated. Emboss Matcher was used to perform sequence alignment between mTG and various antigens implicated in many autoimmune diseases. Monoclonal and polyclonal antibodies made specifically against mTG were applied to 77 different human tissue antigens using ELISA. Six antigens were detected to share significant homology with mTG immunogenic sequences, representing major targets of common autoimmune conditions. Polyclonal antibody to mTG reacted significantly with 17 out of 77 tissue antigens. This reaction was most pronounced with mitochondrial M2, ANA, and extractable nuclear antigens. The results indicate that sequence similarity and cross-reactivity between mTG and various tissue antigens are possible, supporting the relationship between mTG and the development of autoimmune disorders 150W.

Cross‐reaction mediated by distinct key amino acid combinations in the complementary‐determining region (CDR) of a monoclonal antibody

“…In our study, we focused on the H1‐74 mAb, targeting the influenza virus HA antigen, and its binding to two specific antigenic epitope peptides, 191‐LVLWGIHHP‐199 and 307‐LPFQNI‐312 10 . We combined bioinformatics analysis with the classical ELISA method to investigate the mechanism of antibody cross‐reaction 24,25 …”

“…10 We combined bioinformatics analysis with the classical ELISA method to investigate the mechanism of antibody cross-reaction. 24,25 In our comparison of the peptides 191-LVLWGIHHP-199 and 307-LPFQNI-312, we identified a common "LXXXXI" structure (Figure 1A), suggesting they might represent similar conformational epitopes. To explore if H1-74 mAb could bind to two distinct short peptides with different conformations, we created a new structure to replace the "LXXXXI" structure in LI-6.…”

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

“…Their presence in a gut luminal cellular compartment presents new opportunities for HGT, with the risk of inhabiting eukaryotic hosts [ 1 , 52 , 53 ]. One of the hypothetical scenarios is the acquisition of a classic microbial survival factor, such as a Trojan horse, against host self-defense barriers [ 1 , 25 , 26 , 54 ]. This gene exchange can happen through mechanisms like plasmid transfer or the incorporation of the transglutaminase gene into a MGE that can be transferred between bacteria.…”

“…Finally, the fact that mTG is a bacterial survival factor can represent a significant positive selective pressure in the harsh, overcrowded luminal compartment [ 1 , 2 ], enhancing its HGT to other intestinal prokaryotic dwellers. It can be summarized that the mTG acts as a double-edged sword, protecting the microbes to survive in the gut lumen, hence compromising human health [ 24 , 25 , 26 , 54 ].…”

“…Type 1 diabetes, multiple sclerosis, celiac disease and psoriasis are some of them [ 88 ]. The above-cited mTG is also associated with AD evolution [ 24 , 25 , 26 , 34 , 36 , 54 , 73 , 77 ]. Intriguingly, the cross-reactive antibodies and sequence similarity between microbial transglutaminase and human tissue antigens were recently reported [ 54 ].…”