Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the lung: epitope reconstitution with peptides extracted from HLA-Aw68.

Cytotoxic T-lymphocytes (CTLs) specific for autologous human squamous cell cancer of the lung were generated by stimulation of peripheral blood lymphocytes with autologous tumor cells in vitro. The CTL line was >97% CD3+, CD8+, CD16- and produced tumor necrosis factor-alpha, gamma-interferon, and granulocyte-macrophage colony-stimulating factor after stimulation with autologous tumor. The CTLs lysed autologous tumor but failed to recognize autologous or histocompatibility leukocyte antigen-matched lymphoid cells, K562, or allogeneic tumor cells of several histological types. Antibody-blocking studies suggested that the CTLs recognized one or more antigens presented by the class I major histocompatibility complex molecule Aw68. To characterize these antigens further, histocompatibility leukocyte antigen Aw68 molecules were extracted from the squamous cell cancer of the lung tumor line by immunoaffinity chromatography, and the associated peptides were eluted in acid and separated by reversed-phase high-performance liquid chromatography. Reconstitution of the CTL epitope was evaluated by adding these peptides to autologous Epstein-Barr virus-transformed B-cells. Two peaks of reconstituting activity were observed, suggesting that these CTLs recognize at least two Aw68-associated peptides. This study confirms the existence of a CTL response against autologous human squamous cell cancer of the lung and suggests that this CTL response is directed against peptide epitopes presented by the class I major histocompatibility complex molecules. It is anticipated that this approach will permit identification of peptide epitopes for lung cancer-specific CTLs.

[1]  R. Henderson,et al.  Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. , 1994, Science.

[2]  M. Frazier,et al.  Cytotoxic T‐Cell Clones Isolated from Ovarian Tumour Infiltrating Lymphocytes Recognize Common Determinants on Non‐Ovarian Tumour Clones , 1993, Scandinavian journal of immunology.

[3]  F. Chisari,et al.  HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis , 1993, The Journal of experimental medicine.

[4]  S. Rosenberg,et al.  Specific release of cytokines by lymphocytes infiltrating human melanomas in response to shared melanoma antigens. , 1993, Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy.

[5]  Don C. Wiley,et al.  Atomic structure of a human MHC molecule presenting an influenza virus peptide , 1992, Nature.

[6]  H. Eisen,et al.  A naturally occurring peptide recognized by alloreactive CD8+ cytotoxic T lymphocytes in association with a class I MHC protein , 1992, Cell.

[7]  P. Parham,et al.  The HLA-A,B "negative" mutant cell line C1R expresses a novel HLA-B35 allele, which also has a point mutation in the translation initiation codon. , 1992, Journal of immunology.

[8]  R. Henderson,et al.  Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. , 1992, Science.

[9]  B. Walker,et al.  An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[10]  P. Cresswell,et al.  Class I-induced resistance to natural killing: identification of nonpermissive residues in HLA-A2. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Rosenberg,et al.  Common Expression of Melanoma Tumor-Associated Antigens Recognized by Human Tumor Infiltrating Lymphocytes: Analysis by Human Lymphocyte Antigen Restriction , 1991, Journal of immunotherapy : official journal of the Society for Biological Therapy.

[12]  R. Bast,et al.  Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. , 1991, Cancer research.

[13]  R. Freedman,et al.  Cytotoxic T cell clones isolated from ovarian tumor-infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells. , 1991, Journal of immunology.

[14]  E. Holmes,et al.  Differential regulation by interleukin-4 and interferon-gamma of an autologous melanoma-specific cytotoxic T-cell clone and the tumor-infiltrating lymphocytes from which it was established. , 1990, Cancer communications.

[15]  K. Meyer zum Büschenfelde,et al.  Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens , 1989, The Journal of experimental medicine.

[16]  C. Slingluff,et al.  Melanoma-specific cytotoxic T cells generated from peripheral blood lymphocytes. Implications of a renewable source of precursors for adoptive cellular immunotherapy. , 1989, Annals of surgery.

[17]  N. Chakraborty,et al.  Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma , 1989, The Journal of experimental medicine.

[18]  C. Slingluff,et al.  The role of HLA class I antigens in recognition of melanoma cells by tumor-specific cytotoxic T lymphocytes. Evidence for shared tumor antigens. , 1989, Journal of immunology.

[19]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[20]  Y. Wei,et al.  In situ observation of lymphocyte-tumor cell interaction in human lung carcinoma. , 1989, Immunological investigations.

[21]  C. Slingluff,et al.  Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases. , 1988, Journal of the National Cancer Institute.

[22]  V. Engelhard,et al.  Cytotoxic T lymphocytes from HLA-A2 transgenic mice specific for HLA-A2 expressed on human cells , 1988, Journal of Experimental Medicine.

[23]  R. Metzgar,et al.  Human tumor-specific cytotoxic T cell lines generated from tumor-draining lymph node infiltrate. , 1988, Transplantation proceedings.

[24]  U. Virginia.  CYTOTOXIC T LYMPHOCYTES FROM HLA-A2 TRANSGENIC MICE SPECIFIC FOR HLA-A2 EXPRESSED ON HUMAN CELLS , 1988 .

[25]  R. Blumberg,et al.  Functional characterization of T lymphocytes propagated from human lung carcinomas. , 1986, Clinical immunology and immunopathology.

[26]  R. Hay.  American Type Culture Collection catalogue of cell lines and hybridomas , 1985 .

[27]  T. Fujisawa,et al.  Cytotoxicity of autologous and allogeneic lymphocytes against cultured human lung cancer cells: optimal conditions for the production of cytotoxic lymphocytes. , 1984, Gan.

[28]  V. Engelhard,et al.  Isolation and characterization of monoclonal mouse cytotoxic T lymphocytes with specificity for HLA-A,B or -DR alloantigens. , 1982, Journal of immunology.

[29]  G. Bonnard,et al.  Human tumour antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells , 1982, Nature.

[30]  P. Parham,et al.  Partial purification and some properties of BB7.2. A cytotoxic monoclonal antibody with specificity for HLA-A2 and a variant of HLA-A28. , 1981, Human immunology.

[31]  S. Rosenberg,et al.  Lysis of human solid tumors by autologous cells sensitized in vitro to alloantigens. , 1981, Journal of immunology.

[32]  L. Lampson,et al.  Two populations of Ia-like molecules on a human B cell line. , 1980, Journal of immunology.