HUMAN PEPTIDE TRANSPORTER DEFICIENCY - IMPORTANCE OF HLA-B IN THE PRESENTATION OF TAP-INDEPENDENT EBV ANTIGENS

Two siblings with a peptide TAP deficiency were recently described, De spite poor cell surface expression of HLA class I molecules, these pat ients were not unusually susceptible to viral infections, The majority of the cell surface-expressed class I molecules were HLA-B products a s assessed by cytofluorometry and biochemical analysis, Analysis of tw o peptides eluted from the class I molecules expressed by TAP-deficien t EBV B lymphoblastoid cell lines indicated that both were derived fro m cytosolic proteins and presented by HLA-B molecules, Peripheral alph a beta CD8(+) T cells were present and their TCR repertoire was polycl onal, Most of the alpha beta CD8(+) T cell clones studied (21 of 22) w ere nonreactive against cells expressing normal levels of the same HLA alleles as those of the TAP-deficient patients. However, it was possi ble to isolate one cytotoxic CD8(+) alpha beta T cell clone recognizin g the EBV protein LMP2 presented by HLA-B molecules on TAP-deficient c ells, These observations suggest that in the TAP-deficient patients, C D8(+) alpha beta T cells could mature and be recruited in immune respo nses 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 previous ly shown to contain several other TAP-independent epitopes.