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

Clin Exp Immunol. 2002 Jun;128(3):525-31. doi: 10.1046/j.1365-2249.2002.01862.x.


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+ alphabeta T cells are almost normal in these patients. The anti-EBV T-cell response of one patient is mediated by HLA-B7 restricted CD8+ alphabeta T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating that CD8+ alphabeta 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / immunology
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Transformed
  • Female
  • Gene Deletion*
  • Genotype
  • HLA-B7 Antigen / immunology
  • HeLa Cells
  • Herpesvirus 4, Human / immunology
  • Histocompatibility Antigens Class I / blood*
  • Histocompatibility Antigens Class I / classification
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Mutagenesis
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • HLA-B7 Antigen
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • TAP2 protein, human