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

Area of Science:

• Immunology
• Human Genetics
• Molecular Biology

Background:

• Human Leukocyte Antigen (HLA) class I deficiency is a rare disorder often caused by defects in the peptide transporter associated with antigen processing (TAP).
• TAP deficiency typically presents with chronic respiratory inflammation or granulomatous skin lesions.

Observation:

• Two adult siblings with HLA class I deficiency due to a homozygous TAP2 mutation were studied.
• One sibling presented with resolving skin granulomas, while the other was asymptomatic.
• Patients exhibited reduced but higher cell surface HLA class I expression compared to previously reported TAP-deficient individuals.

Findings:

• The TAP2 mutation impaired HLA class I molecule maturation, leading to significantly reduced cell surface expression.
• Higher HLA class I expression, partly due to peptide-empty HLA-B7 molecules, was observed.
• Anti-Epstein-Barr virus (EBV) T-cell responses in one patient were mediated by HLA-B7 restricted CD8+ T cells, indicating functional anti-viral immunity.

Implications:

• TAP deficiency can be asymptomatic for extended periods, challenging traditional clinical presentations.
• The findings suggest that TAP-independent immune responses can effectively protect against common intracellular pathogens.
• This highlights the adaptability of the immune system and potential alternative antigen presentation pathways.