Peptide HER2(776-788) represents a naturally processed broad MHC class II-restricted T cell epitope.

作者: R Sotiriadou , S A Perez , A D Gritzapis , P A Sotiropoulou , H Echner

DOI: 10.1054/BJOC.2001.2089

关键词:

摘要: HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designated HER2(776-788)]. Such yielded specific proliferative cytokine [gamma-interferon(IFN)-gamma] responses when challenged with autologous dendritic cells (DCs) loaded HER2(776-788). By performing blocking studies monoclonal antibodies (MAbs) by using DCs from allogeneic donors sharing certain HLA-DR alleles, found that HER2(776-788) is promiscuous presented, at least, DRB5*0101, DRB1*0701 DRB1*0405 alleles. One TCRV beta 6.7+ clone recognized HLA-DRB5*0101+ FM3 melanoma line transfected full length HER-2/neu cDNA. Moreover, this HER-2/neu+ SKBR3 breast cancer induced to express HLA-DR, thus demonstrating represents naturally processed presented epitope. Our data demonstrate epitope binding least three offering broad population coverage. The use antigenic major histocompatibility complex (MHC) II in addition those I may improve therapeutic efficacy active immunization.

参考文章(39)
F Borras-Cuesta, D Zeliszewski, C Freidel, G Sterkers, H Betuel, J J Golvano, L Gebuhrer, P Gaudebout, I Dorval, Implication of HLA-DR residues at positions 67, 71, and 86 in interaction between HLA-DR11 and peptide HA306-320. Journal of Immunology. ,vol. 151, pp. 6237- 6247 ,(1993)
D C Linehan, S O Rogers, T J Eberlein, G E Peoples, P S Goedegebuure, Tumor-specific and HLA-A2-restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer. Journal of Immunology. ,vol. 155, pp. 4486- 4491 ,(1995)
Mary L. Disis, Martin A. Cheever, HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Advances in Cancer Research. ,vol. 71, pp. 343- 371 ,(1997) , 10.1016/S0065-230X(08)60103-7
I Yoshino, T J Eberlein, A S Parikh, G E Peoples, P S Goedegebuure, H K Lyerly, A F Gazdar, J M DiMaio, HER2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. Cancer Research. ,vol. 54, pp. 3387- 3390 ,(1994)
Antonio Lanzavecchia, Paola Panina-Bordignon, Robert W. Karr, Wei Yuan Yu, Antigen-specific T cells with monogamous or promiscuous restriction patterns are sensitive to different HLA-DR beta chain substitutions. Journal of Immunology. ,vol. 146, pp. 4242- 4247 ,(1991)
J D Hayball, R Busch, C M Hill, J R Lamb, J B Rothbard, Effect of natural polymorphism at residue 86 of the HLA-DR beta chain on peptide binding. Journal of Immunology. ,vol. 147, pp. 1292- 1298 ,(1991)
Hubert Kalbacher, Alexei F. Kirkin, Graham Pawelec, Helmut E. Meyer, Thomas Halder, Li Kun, Jesper Zeuthen, Isolation of Novel HLA-DR Restricted Potential Tumor-associated Antigens from the Melanoma Cell Line FM3 Cancer Research. ,vol. 57, pp. 3238- 3244 ,(1997)
Roger Moe, Mary L. Disis, Ann E. Murphy, Robert B. Livingston, Margit Jeschke, Elaine McGlynn, Wei Chen, Martin A. Cheever, Emanuel Calenoff, Graham McLaughlin, Nick Lydon, Bernd Groner, Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Research. ,vol. 54, pp. 16- 20 ,(1994)
Robert W. Karr, Xin Ting Fu, Jeffrey S. McKinney, Craig Swearingen, Ellen Klohe, Ellen Klohe, Individual effects of the DR11-variable beta-chain residues 67, 71, and 86 upon DR(alpha,beta 1*1101)-restricted, peptide-specific T cell proliferation. Journal of Immunology. ,vol. 153, pp. 5564- 5571 ,(1994)
C G Ioannides, S Rashed, R S Freedman, C D Platsoucas, Y P Kim, Cytotoxic T cell clones isolated from ovarian tumor-infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells. Journal of Immunology. ,vol. 146, pp. 1700- 1707 ,(1991)