Single H2K b , H2D b and double H2K b D b homozygous knockout (KO) mice were generated and their peripheral CD8 + T cell repertoires compared to that of C57BL/6 (B6) mice. Limited (10-20 %, H2D b), substantial (30-50 %, H2K b) and profound (90 %, H2K b D b) reduction of peripheral CD8 + T cells was observed in KO mice, without V g diversity alteration. Classical class Ia molecules therefore ensure most but not all of the peripheral CD8 + T cell repertoire education. As expected, H2K b but also H2D b KO mice developed choriomeningitis following intracranial infection by lymphocytic choriomeningitis virus with the same kinetics, lethality and CD8 + cell implication as wild-type B6 mice. By contrast, H2K b D b (class Ia-Ib +) KO mice survived. Choriomeningitis of H2D b KO mice was linked to the development of a subdominant (in normal B6 mice) H2K b-restricted cytotoxic T lymphocyte response. Mice expressing a restricted set of histocompatibility class I molecules should represent useful tools to evaluate the immunological potentials of individual MHC class I molecules.