Table 1.

Evidence for antigen-specific mechanisms in obesity-associated IR.

	Source
Direct evidence of antigen-specific pathology
MHC-II presentation of antigen is necessary for metabolic defects	[61, 62, 98]
VAT-specific TCR repertoire restriction in obese IR mice	[22, 34, 44]
Expansion of effector memory T cells is MHC-II dependent	[98]
Regulation of glucose intolerance is not achieved by transfer of CD4+ OT-2 T cells	[22]
Transfer of disease by antibody is dependent on metabolic status of source and recipient mice	[40]
Insulin resistant and insulin sensitive individuals have distinct IgG autoantibody signatures	[40]
Indirect evidence of antigen-specific activation
Enrichment of antibody within crown-like structures	[40]
Enrichment of T cells within crown-like structures	[10]
Expansion of effector memory T cells in obesity is specific to the adipose tissue	[43, 98]
Antibody class switching is increased in obesity	[40]
Contradictory evidence
No HLA linkage in type 2 diabetes	[99]
No T cell or B cell specific genes linked to type 2 diabetes	[100, 101]
Costimulation is beneficial for glucose metabolism or lack of costimulation worsens glucose metabolism	[102–104]