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Defective presentation of MHC class I‐restricted cytotoxic T‐cell epitopes in Burkitt's lymphoma cells
Author(s) -
Frisan Teresa,
Zhang QianJin,
Levitskaya Jelena,
Coram Michael,
Kurilla Michael G.,
Masucci Maria G.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961009)68:2<251::aid-ijc19>3.0.co;2-d
Subject(s) - epitope , cytotoxic t cell , biology , mhc class i , antigen presentation , antigen processing , antigen , virology , ctl* , major histocompatibility complex , human leukocyte antigen , transporter associated with antigen processing , microbiology and biotechnology , cd8 , immunology , in vitro , biochemistry
Defects of antigen processing/presentation have been suggested to play a role in the escape of Burkitt's lymphoma (BL) from cytotoxic T lymphocyte (CTL)‐mediated rejection. Impaired presentation of an immunodominant HLA AII‐restricted epitope from the resident or recombinant vaccinia virus‐expressed Epstein‐Barr virus nuclear antigen (EBNA)4 was demonstrated in the EBV‐positive E95B‐BL28 and its EBV‐negative parental BL28 cell lines. We have investigated whether this was due to (i) impaired production of the antigenic peptide, (ii) poor peptide translocation into the ER lumen or (iii) inefficient maturation and transport of the MHC‐peptide complexes at the cell surface. The defect was not overcome by cytosolic expression of a pre‐formed epitope, suggesting that presentation of EBNA4 is not limited by inefficient production of the antigenic peptide. BL28 expressed 5‐ to 10‐fold lower levels of the transporter associated with antigen presentation (TAP) 1 and TAP2 proteins and behaved poorly in a streptolysin‐O‐mediated peptide translocation assay, whereas E95B‐BL28 showed higher TAP expression and virtually normal transporter function. Up‐regulation of HLA AII and reconstitution of TAP activity by treatment with IFN‐γ did not restore presentation of the resident EBNA4 in E95B‐BL28 and did not enhance presentation of the vaccinia virus‐expressed intact protein or preformed epitope. Efficient maturation of class I molecules to Endo H‐resistant species was demonstrated in pulse‐chase experiments. Taken together, our findings identify a previously uncharacterized defect of antigen presentation which appears to affect events occurring after proteasomal degradation but before TAP‐dependent peptide transport and MHC class I assembly and maturation. © 1996 Wiley‐Liss, Inc.