HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1

The transporter associated with antigen processing (TAP), which is composed of two subunits (TAP1 and TAP2) that have different biochemical and functi onal properties, plays a key role in peptide loading and the cell surface e xpression of HLA class I molecules. Three cases of HLA class I deficiency h ave previously been shown to result from the absence of a functional TAP2 s ubunit. In the present study, we analyzed two cases displaying not only the typical lung syndrome of HLA class I deficiency but also skin lesions, and found these patients to be TAP1-deficient. This defect leads to unstable H LA class I molecules and their retention in the endoplasmic reticulum. Howe ver, the absence of TAP1 is compatible with life and does not seem to resul t in higher susceptibility to viral infections than TAP2, deficiency. This work also reveals that vasculitis is often observed in HLA class I-deficien t patients.