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.