Promiscuity of MHC class Ib-restricted T cell responses.
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.
Ploss
Alexander
A
Infectious Diseases Service, Department of Medicine and Laboratory of Antimicrobial Immunity, Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Lauvau
Gregoire
G
Contos
Brian
B
Kerksiek
Kristen M
KM
Guirnalda
Patrick D
PD
Leiner
Ingrid
I
Lenz
Laurel L
LL
Bevan
Michael J
MJ
Pamer
Eric G
EG
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007275:Injections, Intravenous; D008024:Ligands; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017384:Sequence Deletion; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
D018984:Epitopes, T-Lymphocyte; C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D008024:Ligands