TAP1-DEFICIENT MICE SELECT A CD8(-CELL REPERTOIRE THAT DISPLAYS BOTH DIVERSITY AND PEPTIDE SPECIFICITY() T)

Mice deficient in the gene encoding the transporter associated with an tigen processing 1 (TAP1) are defective in providing major histocompat ibility complex (MHC) class I molecules with cytosolic peptides. Conse quently, these mice express reduced levels of MHC class I glycoprotein s on the cell surface, and have reduced numbers of CD8(+) T cells in t he periphery. In the present study, we have addressed the diversity an d specificity of the peripheral CD8(+) T cell population in TAP1 -/- m ice. CD8(+) T cells were polyclonal with regard to T cell receptor (TC R) V beta expression. Overall, V beta usage in TAP1 -/- mice appeared to be very similar to that in wild-type mice, with significantly reduc ed levels of V beta 5.1/5.2-expressing CD8(+) T cells as the only clea r exception. This polyclonal population of CD8(+) T cells readily moun ted epitope-specific CTL responses against four out of five well-defin ed MHC class I-restricted peptides. In contrast to allospecific CTL, p eptide-specific CTL from TAP1 -/- mice did not crossreact on cells exp ressing normal levels of H-2(h) class I. The present results demonstra te that a polyclonal CD8(+) T cell repertoire. displaying both diversi ty and peptide specificity, is positively selected in mice devoid of a functional peptide transporter. These observations imply that TAP-dep endent peptides are not absolutely required for positive selection of a functionally diverse repertoire of CD8(+) T cells.