Impaired immune responses and altered peptide repertoire in tapasin-deficient mice.
Tapasin is a component of the major histocompatibility complex (MHC) class I antigen-loading complex. Here we show that mice with a disrupted tapasin gene display reduced MHC class I expression. Cytotoxic T cell (CTL) responses to viruses are impaired, and dendritic cells of tapasin-deficient mice do not cross-present protein antigen via the MHC class I pathway, indicating a defect in antigen processing. Natural killer (NK) cells from tapasin-deficient mice have an altered repertoire and are self-tolerant. In addition, the repertoire of class I-bound peptides is altered towards less stably binding ones. Thus tapasin plays a role in CTL and NK immune responses and in optimal peptide selection.
Garbi
N
N
Division of Molecular Immunology, German Cancer Research Center, im Neuenhelmer Feld 280, D-69120 Heidelberg, Germany.
Tan
P
P
Diehl
A D
AD
Chambers
B J
BJ
Ljunggren
H G
HG
Momburg
F
F
Hämmerling
G J
GJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017920:Antiporters / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D017920:Antiporters; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin