Impaired immune responses and altered peptide repertoire in tapasin-deficient mice

• Published in: Nature immunology Vol. 1; no. 3; pp. 234 - 238
• Main Authors: Hämmerling, Günter J, Garbi, Natalio, Tan, Pamela, Diehl, Alexander D, Chambers, Benedict J, Ljunggren, Hans-Gustaf, Momburg, Frank
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2000
• Subjects: Animals; Antigen Presentation - immunology; Antigen processing; Antiporters - genetics; Antiporters - immunology; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; H-2 Antigens - immunology; H-2 Antigens - metabolism; Histocompatibility Antigen H-2D; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Immune Tolerance - immunology; Immunoglobulins - deficiency; Immunoglobulins - genetics; Immunoglobulins - immunology; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Lymphocytes T; Major histocompatibility complex; Medicin och hälsovetenskap; Membrane Transport Proteins; Mice; Mice, Knockout; Natural killer cells; Peptides; Peptides - immunology; Peptides - metabolism; Phenotype; T-Lymphocytes, Cytotoxic - immunology; Tapasin
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/79775

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.