Consequences of Antigen Self-Presentation by Tumor-Specific Cytotoxic T Cells

doi:10.1016/S0171-2985(00)80088-1

Immunobiology

Volume 201, Issues 3–4, January 2000, Pages 332-346

https://doi.org/10.1016/S0171-2985(00)80088-1 Get rights and content

Abstract

CDS-positive cytotoxic T cells (CTL) recognize antigenic peptides in combination with major histocompatibility complex (MHC) class I molecules on the surface of syngeneic antigen presenting cells (APC). In the present paper we show that cells from tumor antigen-specific CTL clones present their cognate antigenic peptide to other CTL from the same clone. Inter-CTL peptide presentation resulted in activation of the cells of one CTL clone to MHC-unrestricted lysis of bystander cells. In contrast to the behaviour of this clone, another CTL clone did not lyse bystander cells after incubation with the cognate peptide, but was activated to self-destruction. The human herpes virus Epstein-Barr virus is involved in the pathogenesis of a broad spectrum of human neoplasias. Using freshly established non-clonal T cells with specificity for a peptide derived from an Epstein-Barr virus encoded antigen we found again lysis of MHC mismatched bystander cells as a consequence of inter-CTL peptide presentation, indicating that bystander lysis following antigen self-presentation is not a phenomenon restricted to long-term in vitro cultured T cell clones. The potential implications for immunosurveillance against cancer and for tumor escape mechanisms are discussed.

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Citation Excerpt :
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CD8⁺ T-lymphocytes recognize peptides in the context of major histocompatibility complex (MHC) class I antigens. Upon activation, these cells differentiate into effector cytotoxic T lymphocytes (CTL) and no longer require formal antigen presentation by professional antigen presenting cells (APC). Subsequently, any cell expressing MHC class I/cognate peptide can stimulate CTL. Using TIL specific for a melanoma antigen-derived peptide, IMDQVPFSV (g209 2M), we sought to determine whether these CTL could present peptide to each other. Our findings demonstrate that peptide presentation of the g209 2M peptide epitope by TIL is comparable to conventional methods of using T2 cells as APC. We report here that CTL are capable of self-presentation of antigenic peptide to neighboring CTL resulting in IFN-γ secretion, proliferation, and lysis of peptide-loaded CTL. These results demonstrate that human TIL possess both APC functions as well as cytotoxic functions and that this phenomenon could influence CTL activity elicited by immunotherapy.
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^***: Prof. Dr. Angelika B. Reske-Kunz, Klinische Forschergruppe Allergie, Universitäts-Hautklinik/Verfügungsgebäude, Obere Zahlbacher Str. 63, D - 55131 Mainz, Germany, Phone: +49-61 31-17 33 49, Fax: +49-61 31-17 33 64,

^*: Present address: Faculty of Chemistry, Biochemistry II, University of Bielefeld, D - 33615 Bielefeld, Germany

^**: Present address: Molecular Immunology Group, Institute of Molecular Medicine, John Radcliff Hospital, Headington, OX3 9DU, UK

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Consequences of Antigen Self-Presentation by Tumor-Specific Cytotoxic T Cells

Abstract

Immunol. Today

Blood

Today

Virology

antigen recognition

Class discrimination in the world of immunology. Nature

Enterobacteria infected T cells as antigen presenting cells for cytotoxic CDS+ T cells: A contribution to the self-limitation of cellular immune reactions in reactive arthritis? J

Infect. Dis.

Major histocompatibility complex class I-restricted activation of cloned T cells by a soluble protein in the absence of accessory cells

Proc. Natl. Acad. Sci. USA

The antigen self-presentation function of the cytotoxic T cell clone 10BK.1 depends on reciprocal peptide presentation

Immunology

Manifestation of the MHC-unrestricted killing potential of a cytotoxic T cell clone requires activation in response to MHC-restricted self-presentation of antigen

J. Immunol.

Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection

Eur. J. Immunol.

Suppression of MHC class I antigens in oncogenic transformants: association with decreased recognition by cytotoxic T lymphocytes

Exp. Hematol.

Cognate peptides induce self-destruction of CD8+ cytolytic T lymphocytes

Proc. Natl. Acad. Sci. USA

Rapid visual assay of cytotoxic T cell specificity utilizing synthetic peptide induced T cell-T cell killing

Immunology

Influenza peptide-induced self-lysis and down-regulation of cloned cytotoxic T cells

Immunology

Escape mechanisms of melanoma from immune system by soluble melanoma antigen

J. Immunol.

Neutral proteinases of human mononuclear phagocytes. Cellular differentiation markedly alters cell phenotype for serine proteinases, metalloproteinases, and tissue inhibitor of metalloproteinases

J. Immunol.

Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules

Proc. Natl. Acad. Sci. USA

A p16INK4A-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma

Science

Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes

Eur. J. Immunol.

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. J. Exp. Med.

Analysis of antigens recognized on human melanoma cells by A2-restricted cytolytic T lymphocytes (CTL)

Int. J. Cancer

Generation of human B lymphoblastoid cell lines using Epstein-Barr virus

B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2

EMBO J.

Characterization of two Epstein-Barr virus epitopes restricted by HLA-B7

Eur. J. Immunol.

Cognate peptides induce self-destruction of CD8⁺ cytolytic T lymphocytes

A p16^INK4A-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma