Table 1.

Antigenic cross-reactivity between autoimmune disease relevant autoantigens and gut/oral microbial T-cell antigens.

Autoimmune Disease	Species	T Cell Response	Autoantigen	Tissue Expression	Peptide	Epitope	Bacteria Species Crossreactivity	Tissue Location	Bacterial Antigen	MHC Restriction	Evidence	Reference
Rheumatoid Arthritis	Human	CD4+	N-acetylglucosamine-6-sulfatase (GNS)	Synovial tissue	p222-235	FEPFFMMIATPAPH	Prevotella spp.	Gut and oral cavity	Arylsulfatase	ND	Patients show reactivity against autoreactiveand bacterial epitopes	(50)
							Butyricimonas spp.	Gut	Commensal peptide
	Human	CD4+	Filamin A (FLNA)	Synovial tissue	p2446-2460	NPAEFVVNTSNAGAG	Prevotella spp.	Gut and oral cavity	Commensal peptide	ND	RA patients show reactivity against autoreactiveand bacterial	(50)
											epitopes
							Parabacteroides spp.	Gut	Commensal peptide
Anti-phospholipid Syndrome	Human	CD4+	Beta-2 glycoprotein I (b2GPI)	Plasma, binds to endothelial cells	p276-290	KVSFFCKNKEKKCSY	Roseburia intestinalis	Gut	Commensal peptide	DRB1*04:01	Tetramer reactive CD4+ T cells isolated from blood cross-react with commensal bacteria	(51)
Systemic Lupus Erythematosus and Sjögren's Syndrome	Mouse	CD4+	ND	Ubiquitous	p371-381	FLLAVDVSASM	Capnocytophaga ochracea	Oral Cavity	Commensal peptide	DRB1*0301	T cells isolated from Ro60-immunized DR3-humanized mice recognize commensal epitope	(52)
Type 1 Diabetes	Mouse	CD8+	Islet-specific glucose-6-phosphatase catalytic subunit- related protein (IGRP)	Pancreatic β-cells	p206–214	VYLKTNVFL	B. vulgatus; B. sp. 4_3_47FAA; B. sp. 9_1_42FAA; B. sp. 3_1_33FAA; and B. dorei 5_1_36/D4	Gut	Integrase	H-2–Kd	Bacterial peptide triggers recruitment of low avidity IGRP206-214-reactive CD8+ T cells to the gut and protects mice against colitis	(53)
Primary Biliary Cholangitis	Human	CD4+	Pyruvate dehydrogenase complex PDC-E2	Ubiquitous	p163-176	GDLLAEIETDKATI	Escherichia coli	Gut	Lipoic acid-binding domain of commensal PDC-E2	DRB4 *0101	Specific CD4+ T cell clones isolated from patients crossreact with commensal PDC-E2 protein	(54)
Autoimmune Gastritis	Human	CD4+	Gastric enzyme hydrogen potassium adenosine	Gastric mucosa	p621-635	IRVIMVTGDHPITAK	Helicobacter pylori	Gut	Histidine kinase	DR	Specific CD4+ T cell clones isolated from autoimmune gastritis patients crossreact with multiple H. pylori antigens	(55)
Autoimmune Gatritis			triphosphatase (H+,K+–ATPase)		p781-795	NLKKSIAYTLTKNIP			Dimethyl adenosine transferase
					p46-60	KKEMEINDHQLSVAE			Penicillin-binding protein 2			(55)
					p836-850	KAESDIMHLRPRNPK			LPS biosynthesis protein
					p181-195	VIRDGDKFQINADQL			Acetate kinase
					p241-255	CTHESPLETRNIAFF			Phosphoglucosamine mutase
					p256-270	STMCLEGTAQGLVVN			VirB4 homologue
					p516-530	VMKGAPERVLERCSS			GidA
					p621-635	IRVIMVTGDHPITAK			Porphobilinogen deaminase
Multiple Sclerosis	Human	CD4+	Myelin basic protein (MBP)	Central nervous system	p85-99	ENPVVHFFKNIVTPR	Escherichia coli	Gut	GTP-binding protein engA	DRB1*1501	Commensal peptide activates and drives EAE inflammation in Ob TCR-DR2b mice	(56)
	Human	CD4+	Guanosine diphosphate-L-fucose synthase ((GDP)-L-fucose synthase)	Central nervous system	p161-175	YGCTFTAVIPTNVFG	Akkermansia muciniphila	Gut	Commensal peptide	DRB3*02:02	Identification of guanosine diphosphate (GDP)-L-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid-infiltrating CD4+ T cells from HLA-DRB3- positive patients	(57)
	Mouse	CD4+	Myelin oligodendrocyte glycoprotein (MOG)	Central nervous system	p40-48	YRSPFSRVV	Lactobacillus reuterI	Gut	UvrABC system protein A (UvrA)	I-Ab	L. reuteri encodes peptides that potentially mimic MOG. Mice co-colonized with this strain develop more severe experimental autoimmune encephalomyelitis than germ-free or monocolonized mice	(58)

ND, not determined.