This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "molecular_mimicry_autoimmunity#Cross-Reactive Autoreactive Lymphocyte Activation"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding cell types, biological processes, and causal edges, specialized to their disease context. Key disorder-specific substitutions of the mimic pair: Guillain-Barre syndrome uses Campylobacter jejuni sialylated lipo-oligosaccharide mimicking peripheral-nerve gangliosides (anti-GM1/GD1a/GQ1b); MIS-C uses a SARS-CoV-2 nucleocapsid epitope mimicking the host antiviral-signalling protein SNX8; acute rheumatic fever (not yet a worked conformer) uses streptococcal M protein mimicking cardiac myosin. Susceptibility is frequently gated by HLA alleles that provide the restricting element for presentation of the cross-reactive epitope. Mimic chemistry and specific autoantigens are described in prose only; modules bind GO and CL terms only and do not use gene (HGNC) or chemical (CHEBI) term bindings.
Infection-Associated Cross-Reactive Antigen Exposure
trigger
An infectious agent (or, less commonly, a chemical/environmental antigen) presents an epitope that shares sequence or structural similarity with a host self-antigen. Antigen processing and presentation of this foreign epitope in a susceptible host is the initiating event: because the foreign and self peptides are similar, the immune response mounted against the pathogen is positioned to cross-react with self. The specific mimic pair is disorder-specific (e.g., Campylobacter lipo-oligosaccharide vs nerve gangliosides; SARS-CoV-2 nucleocapsid vs SNX8).
Downstream
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Cross-Reactive Autoreactive Lymphocyte Activation
Show evidence (3 references)
"Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual."
Defines molecular mimicry as an infection/chemical-triggered initiator of autoimmunity arising from foreign/self-peptide similarity in a susceptible host, establishing this trigger node. Evidence source is OTHER because this is a review.
"One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens."
Directly states that the foreign antigen shares sequence or structural similarity with self-antigens, the defining feature of the cross-reactive antigen at this node. Evidence source is OTHER because this is a review.
"The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity."
Worked example of the cross-reactive mimic pair in MIS-C: the SARS-CoV-2 nucleocapsid and the host SNX8 protein share immunogenic sequence similarity. Evidence source is HUMAN_CLINICAL because this is a patient autoantibody/T-cell study.
Cross-Reactive Autoreactive Lymphocyte Activation
central effector
The anti-pathogen response activates autoreactive T and/or B lymphocytes whose receptors recognize both the foreign epitope and the mimicked self-antigen. These cross-reactive clones escaped central tolerance and are expanded by the foreign-derived antigen; cross-reactive B cells secrete autoantibodies and cross-reactive T cells acquire effector function. This is the pivotal, conserved step that converts a normal antimicrobial response into autoreactivity, and is the canonical conformance target for disorders driven by molecular mimicry.
Downstream
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Autoreactive Effector-Mediated Tissue Injury
Show evidence (3 references)
"It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual."
States that the cross-reactive foreign antigen activates autoreactive T or B cells, the central effector event of this node. Evidence source is OTHER because this is a review.
"Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes."
Worked example showing cross-reactive lymphocytes in MIS-C: anti-SNX8 autoantibodies (B-cell output) plus T cells recognizing both the self (SNX8) and foreign (nucleocapsid) epitopes. Evidence source is HUMAN_CLINICAL because this is a patient study.
"These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response."
Describes lymphocytes with dual reactivity to foreign and self-antigens that are triggered into an autoimmune response, supporting cross-reactive autoreactive activation. Evidence source is OTHER because this is a review.
Epitope Spreading and Autoimmune Amplification
amplifier
Effector-mediated tissue damage releases previously sequestered self-antigens that are taken up and presented, priming additional self-reactive T and B clones directed at epitopes distinct from the original mimic (epitope spreading). Together with breach of central tolerance, bystander activation, and persistent antigenic stimulation, this broadens and perpetuates the autoimmune response independent of ongoing infection, converting an initially antigen-restricted reaction into a self-sustaining one.
Downstream
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Tissue-Specific Autoimmune Disease
Show evidence (2 references)
"Evidence continues to accumulate supporting the hypothesis that tissue damage during an immune response can lead to the priming of self-reactive T and/or B lymphocytes, regardless of the specificity of the initial insult."
Establishes epitope spreading: tissue damage primes new self-reactive T/B lymphocytes regardless of the initial trigger, amplifying autoimmunity beyond the original mimic. Evidence source is OTHER because this is a review.
"other factors such as breach in central tolerance, non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to the development of autoimmune diseases."
Lists complementary amplifying mechanisms (tolerance breach, bystander activation, persistent antigen) that, with epitope spreading, sustain the autoimmune response. Evidence source is OTHER because this is a review.
Tissue-Specific Autoimmune Disease
consequence
The cumulative cross-reactive and spread autoimmune attack produces clinical disease localized to the tissue expressing the mimicked self-antigen, with the syndrome defined by which tissue is targeted (e.g., acute polyradiculoneuropathy in Guillain-Barre syndrome, multisystem hyperinflammation in MIS-C, carditis in rheumatic fever). This is the clinical consequence of the conserved molecular-mimicry chain and the level at which conforming disorder entries are defined.
Show evidence (2 references)
"demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases."
Frames the cross-reactive mimicry response as the mechanistic link from infection to a clinical inflammatory syndrome, and generalizes it to a range of post-infectious autoimmune/autoinflammatory diseases, supporting this consequence node. Evidence source is HUMAN_CLINICAL because this is a patient study.
"may also contribute to the development of autoimmune diseases."
Connects the upstream mimicry/tolerance mechanisms to the development of autoimmune disease, the clinical consequence of this module. Evidence source is OTHER because this is a review.