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

Craig L. Slingluff, Andrea Cox, John M. Stover, Marcia M. Moore, Donald F. Hunt, Victor H. Engelhard

Research output: Contribution to journalArticle

Abstract

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-α, γ-interferon, and granulocyte-macrophage colony-stimulating factor after stimulation with autologous tumor. The CTLs lysed autologous tumor but failed to recognize autologous or histocompatability 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, histocompatability 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.

Original languageEnglish (US)
Pages (from-to)2731-2737
Number of pages7
JournalCancer Research
Volume54
Issue number10
StatePublished - May 15 1994
Externally publishedYes

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Squamous Cell Neoplasms
Cytotoxic T-Lymphocytes
Epitopes
Lung Neoplasms
Peptides
Neoplasms
HLA Antigens
Major Histocompatibility Complex
Lymphocytes
HLA-A*68 antigen
Histocompatibility Antigens Class I
Blocking Antibodies
T-Lymphocyte Epitopes
Reverse-Phase Chromatography
Granulocyte-Macrophage Colony-Stimulating Factor
Human Herpesvirus 4
Interferons
Chromatography
B-Lymphocytes
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the lung : Epitope reconstitution with peptides extracted from HLA-Aw68. / Slingluff, Craig L.; Cox, Andrea; Stover, John M.; Moore, Marcia M.; Hunt, Donald F.; Engelhard, Victor H.

In: Cancer Research, Vol. 54, No. 10, 15.05.1994, p. 2731-2737.

Research output: Contribution to journalArticle

Slingluff, Craig L. ; Cox, Andrea ; Stover, John M. ; Moore, Marcia M. ; Hunt, Donald F. ; Engelhard, Victor H. / Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the lung : Epitope reconstitution with peptides extracted from HLA-Aw68. In: Cancer Research. 1994 ; Vol. 54, No. 10. pp. 2731-2737.
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