Table 1.

Autoantigens and autoimmune TCRs in autoimmune diseases.

AD	Species	MHC-II Allele	Antigenic Peptide	Proposed Molecular Mechanisms of AD Susceptibility	Reference
Low-affinity autoantigenic peptides
T1D	Mouse	I-Ag7	Ins. B:12–20, Ins. B:13–21	Weak binding of CLIP by MHC-II molecule promotes loading of low-affinity peptides.	[48]
T1D	Mouse	I-Ag7	Ins. B:12–20, Ins. B:14–22	MHC-II binding of antigenic peptide in a low-affinity register leads to recognition by autoreactive TCRs.	[52,53,54,55]
T1D	Human	HLA-DQA1*03:01, HLA-DQB1*03:02	Ins. B:11–23	MHC-II binding of antigenic peptide in a low-affinity register leads to recognition by autoreactive TCRs.	[56]
Low-affinity autoreactive TCRs
MS	Human	HLA-DRB1*15:01	MBP:85–99	Autoreactive TCRs bind pMHC complexes with low affinity and alternate topology.	[16,67]
MS	Human	HLA-DRB5*01:01	MBP:84–102		[68]
High or intermediate affinity autoreactive TCRs
MS	Human	HLA-DQA1*01:02, HLA-DQB1*05:02	MBP:85–99	The unusual topology of trimolecular complex impedes T cell activation by CD4 receptor.	[70]
MS	Human	HLA-DRB1*04:01	MBP:111–129	Autoreactive TCR stabilizes weak interaction between antigenic peptide and MHC-II.	[72]
EAE	Mouse	I-Au	MBP:1–11 (acetylated)	Autoreactive TCRs bind pMHC complexes with acetylated autoantigens in unusual binding register, where the part of peptide-binding groove is empty.	[73,74,75]

Abbreviations: AD, autoimmune disease; T1D, type 1 diabetes; Ins, insulin; CLIP, class II-associated invariant chain peptide; MS, multiple sclerosis; MBP, myelin basic protein; TCR, T cell receptor; EAE, experimental autoimmune encephalomyelitis.