Asymptomatic deficiency in the peptide transporter associated to antigen processing (TAP)

SUMMARY Human HLA class I deficiency is a rare disease which, in most of the patients described to date, results from a defect in subunit 1 or 2 of the peptide transporter associated with antigen processing (TAP). The clinical features of TAP deficiency include a chronic inflammation of the respiratory tract and/or granulomatous skin lesions. In this report, we describe two adult siblings with an HLA class I deficiency. One individual had only spontaneously‐healing skin granulomatous lesions, while the second did not display any of the symptoms associated with HLA class I deficiency and could be considered to be healthy. We show that the patients display a homozygous TAP2 mutation which blocks the maturation of HLA class I molecules. Cell surface expression of these molecules is strongly reduced, but three times higher than on cells from other previously described TAP‐deficient individuals. This higher expression results, at least in part, from the presence of HLA‐B7 molecules which are probably empty of peptide. The numbers of CD8+αβ T cells are almost normal in these patients. The anti‐EBV T‐cell response of one patient is mediated by HLA‐B7 restricted CD8+αβ T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating that CD8+αβ T cells can participate in anti‐viral responses. This study shows that TAP deficiency can remain totally asymptomatic for several decades, and suggests that in some cases, TAP‐independent immune responses provide efficient protection from most of the common intracellular pathogens.