Identification of a cross-reactive HLA-DRB1*0301-restricted CD4 T cell response directed against cholesterol-binding cytolysins from two different pathogens

Microbes Infect. 2006 Jul;8(8):2034-43. doi: 10.1016/j.micinf.2006.03.010. Epub 2006 May 30.

Abstract

Cholesterol-binding cytolysins constitute an evolutionarily conserved family of pore-forming proteins expressed by different gram-positive pathogens. Listeriolysin O, one well-characterized member of the cytolysin family, is also known to induce specific CD4 and CD8 T cell responses upon infection of mice with Listeria monocytogenes. Here we describe an HLA-DRB1*0301-restricted listeriolysin O-derived T cell epitope that is conserved among several members of the cytolysin family. An HLA-DRB1*0301-restricted CD4+ T cell line, established from spleen lymphocytes of L. monocytogenes-infected HLA-DRB1*0301-transgenic mice, cross-reacted with a homologous peptide from perfringolysin O, a cytolysin expressed by Clostridium perfringens. Ex vivo analysis of infected mice revealed an even broader cross-reaction of T cells with homologous peptides derived from perfringolysin O, streptolysin O, and cereolysin O. Interestingly, a cross-reactive memory CD4+ T cell response against the homologous peptides derived from listeriolysin O and perfringolysin O could also be detected in the blood from healthy HLA-DRB1*0301+ human donors. Remarkably, this response was even present in donors who did not exhibit a memory T cell reactivity against a second, non-conserved HLA-DRB1*0301-restricted LLO-derived CD4 T cell epitope, suggesting that cytolysin-producing bacteria other than L. monocytogenes can stimulate a cross-reactive cytolysin-specific immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / immunology*
  • Bacterial Toxins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cholesterol / metabolism
  • Clostridium perfringens / immunology
  • Cross Reactions
  • Cytotoxins / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • Heat-Shock Proteins / immunology
  • Hemolysin Proteins / immunology
  • Humans
  • Immunologic Memory
  • Interferon-gamma / biosynthesis
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Mice
  • Mice, Transgenic

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Cytotoxins
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*03:01 antigen
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Clostridium perfringens theta-toxin
  • Interferon-gamma
  • Cholesterol
  • hlyA protein, Listeria monocytogenes