Promiscuity of MHC class Ib-restricted T Cell responses Journal Article

Authors: Ploss, A.; Lauvau, G.; Contos, B.; Kerksiek, K. M.; Guirnalda, P. D.; Leiner, I.; Lenz, L. L.; Bevan, M. J.; Pamer, E. G.
Article Title: Promiscuity of MHC class Ib-restricted T Cell responses
Abstract: Murine infection with the Gram-positive intracellular bacterium Listeria monocytogenes activates CD8+ T cells that recognize bacterially derived N-formyl methionine peptides in the context of H2-M3 MHC class Ib molecules. Three peptides, fMIGWII, fMIVIL, and fMIVTLF, are targets of L. monocytogenes-specific CD8+ T cells. To investigate epitope cross-recognition by H2-M3-restricted CD8+ T cells, we deleted the sequence encoding fMIGWII from a virulent strain of L. monocytogenes. Infection with fMIGWII-deficient L. monocytogenes unexpectedly primed CD8+ T cells that stain with fMIGWII/H2-M3 tetramers and lyse fMIGWII-coated target cells in vivo. Because the fMIGWII sequence is nonredundant, we speculated that other bacterially derived Ags are priming these responses. HPLC peptide fractionation of bacterial culture supernatants revealed several distinct L. monocytogenes-derived peptides that are recognized by fMIGWII-specific T cells. Our results demonstrate that the dominant H2-M3-restricted CD8+ T cell population, although reactive with fMIGWII, is primed by other, non-fMIGWII peptides derived from L. monocytogenes. Although this degree of Ag receptor promiscuity is unusual for the adaptive immune system, it may be a more common feature of T cell responses restricted by nonpolymorphic MHC class Ib molecules.
Keywords: controlled study; unclassified drug; sequence analysis; sequence deletion; nonhuman; cd8 antigen; t lymphocyte; cd8-positive t-lymphocytes; protein analysis; animal cell; mouse; animals; mice; cell line; animal experiment; animal model; cell line, tumor; bacterial virulence; mice, inbred c57bl; amino acid sequence; antigen recognition; immunodominant epitopes; epitope; t-lymphocytes, cytotoxic; histocompatibility antigens class i; ligands; cytolysis; target cell; cytotoxicity, immunologic; high performance liquid chromatography; t-lymphocyte subsets; epitopes, t-lymphocyte; bacterium culture; bacterial infection; clone cells; listeria monocytogenes; injections, intravenous; tetramer; major histocompatibility antigen class 1; supernatant; lymphocyte subpopulation; formylmethionine; female; priority journal; article; major histocompatibility antigen class 1b; protein fmigwii; mast-cell sarcoma
Journal Title: Journal of Immunology
Volume: 171
Issue: 11
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2003-12-01
Start Page: 5948
End Page: 5955
Language: English
PUBMED: 14634106
PROVIDER: scopus
PMCID: PMC2791464
DOI: 10.4049/jimmunol.171.11.5948
Notes: Export Date: 12 September 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Alexander Ploss
    7 Ploss
  2. Eric Pamer
    279 Pamer
  3. Ingrid Leiner
    49 Leiner