**1. Introduction**

It is well known that specific human leukocyte antigen (HLA) class II alleles are associated with susceptibility to many autoimmune diseases [1]. However, the mechanisms by which specific HLA class II molecules control the immune response in autoimmune diseases have been unclear. On the other hand, autoantibodies are produced in most autoimmune diseases and cause clinical manifestations of the diseases. It has also been an enigma how autoantibodies targeting self-antigens cause the autoimmune diseases. Arase *et al.* discovered a novel function of HLA class II molecules which are involved in the pathogenesis of certain autoimmune diseases [2–5].

This review will focus on the autoantibodies associating with the novel function of HLA class II molecules and the pathogenesis of antiphospholipid syndrome (APS).
