Molecular Mimicry, Microbial Infection, and Autoimmune Disease: Evolution of the Concept

Abstract

Molecular mimicry is defined as similar structures shared by molecules from dissimilar genes or by their protein products. Either several linear amino acids or their conformational fit may be shared, even though their origins are separate. Hence, during a viral or microbe infection, if that organism shares cross-reactive epitopes for B or T cells with the host, then the response to the infecting agent will also attack the host, causing autoimmune disease. A variation on this theme is when a second, third, or repeated infection(s) shares cross-reactive B or T cell epitopes with the first (initiating) virus but not necessarily the host. In this instance, the secondary infectious agents increase the number of antiviral/antihost effector antibodies or T cells that potentiate or precipitate the autoimmune assault. The formation of this concept initially via study of monoclonal antibody or clone T cell cross-recognition in vitro through its evolution to in vivo animal models and to selected human diseases is explored in this mini-review.

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

“…Autoimmunity often develops subsequent to other injurious processes (e.g., infections, cancer) by "bystander mechanisms," epitope spread or mimicry, or other poorly understood mechanisms (6,(39)(40)(41)(42). In some cases, these "new" autoimmune responses can cause striking additional morbidity (e.g., carditis or nephritis following otherwise self-limited streptococcal infections, neurologic deficit syndromes associated with transient viral infections, neoplasms) (39,40).…”

Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

“…The identity(ies) of the Ag(s) that trigger and fuel these immune processes has not yet been established, although microbes that frequently (and/or chronically) colonize or infect COPD lungs have been indirectly implicated as potential initiators of immune responses (21,28,29). In turn, these antimicrobial responses could possibly generalize via processes of mimicry and/or epitope spreading (30). Autoreactive cellular and humoral responses directed against lung endothelium, epithelium, and connective tissue elements appear to be frequent in COPD patients (26,27), and these processes could also conceivably contribute to or cause systemic manifestations of the disease (22).…”

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

“…In some cases it appears that the molecular characteristics of the inciting antigen resemble or "mimic" those of self-determinants, which then become targets of immune responses that were initially triggered and fueled by the exogenous antigen (Oldstone et al 2005). In addition, highly focused and appropriate responses against foreign antigens can spread to include targeting of otherwise quiescent self-antigens by functional errors of specifi city or "epitope spreading" (Figure 4) (Vanderlugt and Miller 2002).…”

“…As previously described, the lower airways of COPD patients are frequently colonized and/or infected with various microbes (Soler et al 1999;Sethi et al 2006) that are known to be capable of immune activation (Adlovitz et al 2006). Thus, adaptive immune responses that arose to eradicate these organisms could ultimately lead to selfreactivity by processes of microbial mimicry and/or epitope spreading, particularly in patients with chronic exposure to these organisms (Oldstone et al 2005;Vanderlugt and Miller 2002;Croxford et al 2002).…”