Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes.

Introduction: Human leukocyte antigen (HLA) I molecules present antigenic peptides to activate CD8 T cells. Type 1 Diabetes (T1D) is an auto-immune disease caused by aberrant activation of the CD8 T cells that destroy insulin-producing pancreatic β cells. Some alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1D-protective alleles).

Polymorphism in F pocket affects peptide selection and stability of type 1 diabetes-associated HLA-B39 allotypes.

HLA-B*39:06, HLA-B*39:01, and HLA-B*38:01 are closely related HLA allotypes differentially associated with type 1 diabetes (T1D) risk and progression. B*39:06 is highly predisposing, while B*39:01 and B*38:01 are weakly predisposing and protective allotypes, respectively. Here, we aimed to decipher molecular mechanisms underlying the differential association of these allotypes with T1D pathogenesis.