1. Human peptide transporter deficiency: importance of HLA-B in the presentation of TAP-independent EBV antigens
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Delasalle, H., Houssaint, E., Peyrat, Ma, Arnold, D., Salamero, J., Pinczon, D., Stevanovic, S., Bausinger, H., Fricker, D., Gomard, E., Biddison, W., Lehner, P., Uytdehaag, F., Sasportes, M., Donato, L., Rammensee, Hg, Jean-Pierre Cazenave, Hanau, D., Tongio, Mm, Bonneville, M., and Virology
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Immunology ,Immunology and Allergy - Abstract
Two siblings with a peptide TAP deficiency were recently described. Despite poor cell surface expression of HLA class I molecules, these patients were not unusually susceptible to viral infections. The majority of the cell surface-expressed class I molecules were HLA-B products as assessed by cytofluorometry and biochemical analysis. Analysis of two peptides eluted from the class I molecules expressed by TAP-deficient EBV B lymphoblastoid cell lines indicated that both were derived from cytosolic proteins and presented by HLA-B molecules. Peripheral alphabeta CD8+ T cells were present and their TCR repertoire was polyclonal. Most of the alphabeta CD8+ T cell clones studied (21 of 22) were nonreactive against cells expressing normal levels of the same HLA alleles as those of the TAP-deficient patients. However, it was possible to isolate one cytotoxic CD8+ alphabeta T cell clone recognizing the EBV protein LMP2 presented by HLA-B molecules on TAP-deficient cells. These observations suggest that in the TAP-deficient patients, CD8+ alphabeta T cells could mature and be recruited in immune responses to mediate HLA class I-restricted cytotoxic defense against viral infections. They also strengthen the physiologic importance of a TAP-independent processing pathway of the LMP2 protein, which was previously shown to contain several other TAP-independent epitopes.
- Published
- 1997
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