Immune escape of melanoma: first evidence of structural alterations in two distinct components of the MHC class I antigen processing pathway.

Abstract

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.

• Authors: B Seliger, U Ritz, R Abele, M Bock, R Tampé, G Sutter, I Drexler, C Huber, S Ferrone
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 24 Pg. 8647-50 (Dec 15 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11751378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP Binding Cassette Transporter, Subfamily B, Member 3
• ATP-Binding Cassette Transporters
• HLA-A2 Antigen
• TAP1 protein, human
• TAP2 protein, human

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP Binding Cassette Transporter, Subfamily B, Member 3
• ATP-Binding Cassette Transporters (biosynthesis, genetics, immunology)
• Antigen Presentation (immunology)
• Carcinoma, Renal Cell (genetics, immunology, metabolism)
• HLA-A2 Antigen (biosynthesis, genetics, immunology)
• Humans
• Immunologic Surveillance (immunology)
• Kidney Neoplasms (genetics, immunology, metabolism)
• Melanoma (genetics, immunology, metabolism)
• Mutation
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes, Cytotoxic (immunology)
• Transfection
• Tumor Cells, Cultured