INDUCTION OF PEPTIDE-SPECIFIC CD8(-)MICROGLOBULIN-DEFICIENT MICE() CTL CLONES IN BETA(2)

We have examined the ability of beta(2)-m(-) mice to produce CD4(-)8() T cells by generating CD8(+) CTLs to a defined ligand. We report her e the first demonstration of peptide-specific, self-class MHC-restrict ed CTLs from beta(2)-m-deficient mice. We have used the KOD mouse, an H-2(d) beta(2)-m strain, to generate CTLs that recognize the class I M HC molecule L(d) in association with one of two L(d)-binding immunogen ic peptides. Testing of these CTLs on a panel of L(d)-binding peptides reveals a high degree of peptide specificity. Peptide-specific CTL bu lk cultures from KOD mice differ from those generated in beta(2)-m(+) mice in that they possess altered affinities for their peptide ligands . In addition, we show that CTLs-generated from beta(2)-m(-) mice in t he presence of beta(2)-m(+) stimulator cells and exogenous peptide are specific either for the exogenous peptide or for endogenous peptides that are present in association with Ld On the surface of beta(2)-m(+) cells, but are not present at detectable levels on beta(2)-m(-) cells . These results demonstrate that positive selection of CD8(+) CTLs can occur in vivo on the very low levels of class I MHC found in the KOD mouse. Furthermore, CTLs from the KOD mouse maintain a high degree of peptide specificity despite reduced levels of class I MHC.