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) respons
es to viruses are impaired, and dendritic cells of tapasin-deficient mice d
o not cross-present protein antigen via the MHC class I pathway, indicating
a defect in antigen processing. Natural killer (NK) cells from tapasin-def
icient mice have an altered repertoire and are self-tolerant. In addition,
the repertoire of class I-bound peptides is altered towards less stably bin
ding ones. Thus tapasin plays a role in CTL and NK immune responses and in
optimal peptide selection.