HER-2/neu peptide specificity in the recognition of HLA-A2 by natural killer cells |
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Authors: | Larry D. Anderson Jr. J. Michael Hudson Cherylyn A. Savary Bryan Fisk David M. Gershenson Constantin G. Ioannides |
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Affiliation: | (1) The University of Texas M.D. Anderson Cancer Center, Department of Gynecologic Oncology, Box 67, 1515 Holcombe Blvd., Houston, Texas 77030, USA e-mail: ioannides.constantin@gynonc.mdacc.tmc.edu Tel.: +1-713-792-2849 Fax: +1-713-792-7586, US;(2) The University of Texas M.D. Anderson Cancer Center, Department of Surgical Oncology, Box 18, 1515 Holcombe Blvd., Houston, Texas 77030, USA, US |
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Abstract: | Although natural killer (NK) cells have been described as non-MHC-restricted, new evidence suggests that NK activity can be either up- or down-regulated after interaction with the peptide–MHC-class-I complex expressed on target cells. However, the epitope(s) recognized by NK cells have remained ill-defined. We investigated NK cell recognition of synthetic peptides representing a portion of a self-protein encoded by the HER-2/neu (HER-2) proto-oncogene and presented by HLA-A2. HER-2 nonapeptides C85, E89, and E75 were found partially to protect T2 targets from lysis by freshly isolated and interleukin-2(IL-2)-activated NK cells (either HLA-A2+ or A2−). This inhibition was not solely due to changes in the level of HLA-A2 expression or conformation of serological HLA-A2 epitopes. Using single-amino-acid variants at position 1 (P1) of two HER-2 peptides, we observed that protection of targets was dependent on the sequence and the side-chain. These results suggest similarities in the mechanism of target recognition by NK and T cells. This information may be important for understanding the mechanisms of tumor escape from immunosurveillance and could help explain the aggressiveness of HER-2-overexpressing tumor cells. Received: 16 March 1999 / Accepted: 3 June 1999 |
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Keywords: | Natural killer cells HER-2/neu Peptides MHC Tumor immunity |
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