Clinical and Immunological Remarks about TAP Deficiency

We read with interest the article by Lorente et al. (1) describing the presentation of TAP-independent antigens from vaccinia virus by TAP-deficient cells. Their findings offer a mechanistic explanation for the fact that TAP-deficient patients are not particularly susceptible to viral infections and for why adult patients often have normal CD8+ T-cell numbers (2–4). Conversely, severe viral infections might occur early in life, preparing the grounds for the usually observed recurrent bacterial infections. TAP-independent peptides might be generated during most viral infections. However, the presentation of these peptides to CD8+ T-cells to generate efficient antiviral immune responses is still likely to be dependent on the patient's HLA haplotype. Interestingly, HLA-A*02, the most common HLA class I allele in Europe, has been previously shown to present diverse TAP-independent peptides to CD8+ T-cells (5) but has not been found in the clinically immunodeficient patients. Thus, HLA-A*02 homozygous TAP-deficient people might be protected from severe clinical manifestations, thereby “escaping” diagnosis. We suggest slightly modifying the statement that “TAP-deficient patients live normal life spans with only a limited susceptibility to chronic respiratory bacterial infections.” Although we agree that this is possible, patients often suffer from widespread bronchiectasis and respiratory insufficiency. Many develop mutilating granulomatous skin ulcers in the mid-face and on the extremities (2–4). Importantly, treatment with immunosuppressive drugs leads to progression of bronchiectasis, respiratory failure, and complications such as brain abscesses. A question arising is whether TAP plays a role in the presentation of bacterial antigens. Future studies might examine the efficiency of this pathway in TAP-deficient patients.