Identification of antigenic epitopes recognized by Mac-2 binding protein-specific cytotoxic T lymphocytes in an

Keiichi Kontani1, Koji Teramoto, Yoshitomo Ozaki

  • 1Department of Surgery, Shiga University of Medical Science, Seta-tsukinowa, Otsu 520-2192, Japan. konbat@med.kagawa-u.ac.jp

Insights

Researchers identified a new lung cancer immunotherapy target. A specific peptide derived from 90K/Mac-2 binding protein (M2BP) effectively stimulated cytotoxic T lymphocytes (CTLs) in HLA-A24 positive individuals, showing potential for cancer treatment.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • 90K/Mac-2 binding protein (M2BP) is highly expressed in lung cancer.
  • M2BP-specific immunity is observed in many lung cancer patients, suggesting its potential as a therapeutic target.
  • Previous findings indicated M2BP as a potential target antigen for cancer immunotherapy.

Purpose of the Study:

  • To select M2BP-derived peptides with an HLA-A24 binding motif.
  • To analyze the ability of these peptides to induce M2BP-specific cytotoxic T lymphocytes (CTLs).
  • To identify a novel M2BP-derived CTL epitope for lung cancer immunotherapy.

Main Methods:

  • Selected 11 peptides from M2BP with an HLA-A24 binding motif.
  • Generated CTLs using M2BP-derived peptides from CD8-positive T lymphocytes of HLA-A24-positive healthy donors.
  • Assessed CTL response via interferon-gamma production and reactivity against peptide-pulsed cells and cancer cells (TISI and BT20).

Main Results:

  • Two CTLs, induced by M2BP(241-250) and M2BP(568-576), produced interferon-gamma.
  • CTLs induced with M2BP(241-250) reacted with both peptide-pulsed TISI cells and M2BP/HLA-A24 expressing BT20 cells.
  • M2BP(241-250) was identified as a naturally processed epitope recognized by M2BP-specific CTLs in an HLA-A24 restricted manner.

Conclusions:

  • M2BP(241-250) is a naturally processed epitope derived from M2BP in cancer cells.
  • This M2BP-derived peptide is recognized by M2BP-specific CTLs in an HLA-A24 restricted manner.
  • The identified M2BP(241-250) CTL epitope is a promising target for clinical immunotherapy in lung cancer.

Related Concept Videos

Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...