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[Cancer Research 61, 8647-8650, December 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Immune Escape of Melanoma

First Evidence of Structural Alterations in Two Distinct Components of the MHC Class I Antigen Processing Pathway1

Barbara Seliger2, Ulrike Ritz, Rupert Abele, Michaela Bock, Robert Tampé, Gert Sutter, Ingo Drexler, Christoph Huber and Soldano Ferrone

Johannes Gutenberg-University, Third Department of Internal Medicine, 55101 Mainz, Germany [B. S., U. R., M. B., C. H.]; Philipps-University Marburg, Institute of Physiological Chemistry, Medical School, Marburg, Germany [R. A., R. T.]; GSF Research Center, Institute for Molecular Virology, 81675 Munich, Germany [G. S.]; Technical University, Institute for Virology, 81675 Munich, Germany [G. S., I. D.]; and Roswell Park Cancer Institute, Department of Immunology, Buffalo, New York 14263 [S. F.]

Sequence analyses of the transporter associated with antigen processing (TAP) in tumor cell lines with deficient MHC class I surface expression identified a bp deletion at position 1489 near the ATP-binding domain of Tap1, causing a frameshift in one melanoma cell line. The impaired TAP1 protein expression was associated with deficient TAP2 protein expression, peptide binding, translocation, and MHC class I surface expression. Stable TAP1 gene transfer reconstitutes the described defects, whereas lysis by HLA-A2-restricted CTLs was still abrogated. This was attributable to a 2-bp insertion at position 890 in the HLA-A2 gene and was corrected after HLA-A2 cotransfection. This study describes for the first time mutations in two distinct components of the MHC class I antigen processing pathway, suggesting an immune selection against CTLs recognizing both TAP-dependent and -independent T-cell epitopes.




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