Cross-reactivity between cancer and microbial antigens

Figures & data

Table 1. Examples of cross-reactivities between microbial and self-antigens

Pathology	Microbial antigen or modification of self-antigen	Self-antigen	MHC class I + observations	Reference
Antiphospholipid syndrome (APS)	Proteins from Roseburia intestinalis stimulate β2GPI-reactive memory CD4^+ Th1 Cells from APS patients, and one protein (DNMT) crossreacts with a patient-derived anti¯β2GPI mAb	T and B cell autoepitopes in the APS autoantigen β2-glycoprotein I (β2GPI)	HLA-DRB4*0103 (serotype DR53) APS patients have high levels of intestinalis – specific IgG antibodies. Oral gavage of susceptible (NZW × BXSB)F1 mice with R. intestinalis induces anti-human β2GPI autoantibodies and lethal thromboses	^Citation3
Cancer: Multiple transplantable mouse cancers	TSLARFANI contained in the TMP1 protein expressed by an enterococcal phage	GSLARFRNI contained in PSMB4 protein	Mouse K^b Colonization with Enterococcus hirae or Escherichia coli expressing the TMP1 epitope improves control of MCA205 fibrosarcomas	^Citation4
Cancer: Lung adenocarcinoma + kidney cancer	KLAKFASVV contained in the TMP1 expressed by an enterococcal phage	KLQKFASTV contained in GPD1-L protein	HLA-A*0201 Cross-reactive T cells found in non-small cell lung cancer patients. Presence of TMP1 associated to good prognosis in patients treated with PD-1 blockade	^Citation4
Cancer: melanoma	SVYRYYGL expressed by Bifidobacterium breve	SIYRYYGL artificially introduced into B16 melanoma cells	Mouse K^b Colonization with B. breve allows for melanoma control	^Citation5
	Multiple melanoma antigen-homologous peptides identified by bioinformatics within the human intestinal microbiota	EAAGIGILTV present in the MART-1 protein and TLNDECWPA present in MELOE1	HLA-A*0201 In vitro evidence of cross-reactive T cells with defined TCR sequences	^Citation4
Inflammatory cardiomyopathy	FLILMAALTATFASAQ contained in β-galactosidase from Bacteroides thetaiotaomicron and B. faecis	SLKLMATLFSSYATAD from human myosin heavy chain 6 (MYH6)	HLA-DQB1* Bacteroides-specific CD4^+ T cell and B cell responses found in human myocarditis patients. B. thetaiotaomicron monocolonization expressing the β-galactosidase epitope favors myocarditis development in mice expressing a MYH6- specific T cell receptor on more than 95% of their CD4^+ T cells.	^Citation6
Multiple sclerosis (MS)	Akkermansia muciniphila Epstein Barr virus (EBV)	HLA-DR15 DR2a and Dr2b presenting peptides derived from themselves	HLA-DR15 cross-reactive responses between autoreactive CD4^+ T cells from an MS patients and peptides derived from A. muciniphila or EBV, which are both epidemiologically associated with MS	^Citation7
Rheumatoid arthritis (RA)	Citrullination of host proteins following periodontitis by leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strains	Citrullinated host proteins in neutrophils	Shared epitope (SE)-containing HLA-DRB1 alleles. Epidemiological association between anti-Aa antibodies, anti-citrullinated protein antibodies and rheumatoid factor	^Citation8
Systemic lupus erythematosus (SLE)	Skin and mucosal bacteria expressing Ro60, in particular species of Corynebacterium, Propionibacterium, and Bacteroides	Ro60 autoantigen	HLA-DR3 and HLA-DR15 Human Ro60 autoantigen–specific CD4 memory T cell clones from lupus patients are activated by Ro60-containing bacteria. Germ-free mice colonized with a Ro60 ortholog–containing Bacteroides thetaiotaomicron develop T and B cell response against anti-human Ro60, as well as glomerular immune complex deposits.	^Citation9
	Enterococcus gallinarum, which is found in the liver from autoimmune patients and translocates from the gut to the liver in genetically lupus-prone (NZW × BXSB)F1 hybrid mouse	Increased expression of autoantigens ERV gp70 and β2GPI by hepatocytes cultured with E. gallinarum	SLE patients have increased antibodies against E. gallinarum RNA. Germ-free C57Bl/6 mice colonized with E. gallinarum allow for translocation of the bacterium and induces autoantibodies. Intramuscular vaccination of (NZW × BXSB)F1mice with heat-inactivated E. gallinarum attenuates autoimmunity.	^Citation10

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