Morbid Sequences Suggest Molecular Mimicry between Microbial Peptides and Self-Antigens: A Possibility of Inciting Autoimmunity

Abstract

Understanding etiology of autoimmune diseases has been a great challenge for designing drugs and vaccines. The pathophysiology of many autoimmune diseases may be attributed to molecular mimicry provoked by microbes. Molecular mimicry hypothesizes that a sequence homology between foreign and self-peptides leads to cross-activation of autoreactive T cells. Different microbial proteins are implicated in various autoimmune diseases, including multiple sclerosis, human type 1 diabetes, primary biliary cirrhosis and rheumatoid arthritis. It may be imperative to identify the microbial epitopes that initiate the activation of autoreactive T cells. Consequently, in the present study, we employed immunoinformatics tools to delineate homologous antigenic regions between microbes and human proteins at not only the sequence level but at the structural level too. Interestingly, many cross-reactive MHC class II binding epitopes were detected from an array of microbes. Further, these peptides possess a potential to skew immune response toward Th1-like patterns. The present study divulges many microbial target proteins, their putative MHC-binding epitopes, and predicted structures to establish the fact that both sequence and structure are two important aspects for understanding the relationship between molecular mimicry and autoimmune diseases. Such findings may enable us in designing potential immunotherapies to tolerize autoreactive T cells.

TCRβ repertoire of memory T cell reveals potential role for Escherichia coli in the pathogenesis of primary biliary cholangitis

“…A factor related to the involvement of E coli in the onset of PBC is the molecular homology between E coli and humans, as molecular homology is believed to play an important role in the activation of autoreactive T cells . We identified and compared the levels of human PDC‐E2‐specific TCR and E coli PDC‐E2‐specific TCRs in PBC patients and healthy controls.…”

“…A factor related to the involvement of E coli in the onset of PBC is the molecular homology between E coli and humans, as molecular homology is believed to play an important role in the activation of autoreactive T cells. 12,13 We identified and compared the levels of human PDC-E2-specific TCR and E coli PDC-E2-specific TCRs in PBC patients and healthy controls. It was worth noticing that there were many overlaps in the sequences between the TCRs recovered from human PDC-E2 stimulation versus E coli PDC-E2 stimulation.…”

Polymyalgia rheumatica and remitting seronegative symmetrical synovitis with pitting edema following intravesical instillation of bacillus Calmette-Guerin

“…Genetic factors, related to HLA antigens, could be another favoring factor, acting as restriction molecules for antigenic bacterial peptides presented to and cross recognized by cytotoxic CD8+ Tlymphocytes. Furthermore, these peptides possess a potential to skew the immune response toward Th1-like patterns [30].…”

Regulating Gut Microbiome: Therapeutic Strategy for Rheumatoid Arthritis During Pregnancy and Lactation

“…Researches in RA patients or animal models indicated that the abundance of many genera of gut microbiome increased or decreased significantly compared with the control group (healthy people or animal). The influence mechanism of gut microbiome on the pathophysiology of RA may be multifactorial, and it mainly includes the following aspects: the ability to produce citrullinization of peptides by enzymatic action, activation of antigen-presenting cells through an effect on TLRs or NLRs, antigenic mimicry, control of host immune system (triggering T cell differentiation), alterations in permeability of intestinal mucosal, and increase of T helper type 17-mediated mucosal inflammation [Table 1 (Round et al, 2011;Marietta et al, 2016;Teng et al, 2016;Pahari et al, 2017;Guo et al, 2019;Li et al, 2020;McHugh, 2020;Tajik et al, 2020)].…”