**6. Alleles of HLA-DR complexed with β2GPI affect susceptibility to APS**

HLA-DR4, HLA-DR7, and HLA-DR13 have been reported as susceptibility alleles for APS [15–18]. However, the mechanism by which these HLA class II alleles increase susceptibility to APS has remained an enigma.

To address this issue, we analyzed the ability of different HLA-DR alleles to transport β2GPI to the cell surface and found that HLA-DR7 and HLA-DR4 could transport much higher levels of β2GPI than other HLA-DR alleles recognized by the EY2C9 monoclonal antibody [4]. These results indicated that a binding affinity of β2GPI to each HLA-DR allele is important for autoantibody recognition of β2GPI/ HLA-DR complexes and is associated with differences in susceptibility to APS between different HLA-DR alleles.
