Single H2K(b), H2D(b) and double H2K(b)D(b) knockout mice: peripheral CD8(+) T cell repertoire and anti-lymphocytic choriomeningitis virus cytolytic responses

Single H2K(b), H2D(b) and double H2K(b)D(b) homozygous knockout (KO) mice w ere generated and their peripheral CD8(+) T cell repertoires compared to th at of C57BL/6 (B6) mice. Limited (10-20 %, H2D(b)), substantial (30-50 %, H 2K(b)) and profound (90 %, H2K(b)D(b)) reduction of peripheral CD8+ T cells was observed in KO mice, without VP diversity alteration. Classical class la molecules therefore ensure most but not all of the peripheral CD8+ T cel l repertoire education. As expected, H2K(b) but also H2D(b) KO mice develop ed choriomeningitis following intracranial infection by lymphocytic choriom eningitis virus with the same kinetics, lethality and CD8+ cell implication as wild-type B6 mice. By contrast, H2K(b)D(b) (class la(-)lb(+)) KO mice s urvived. Choriomeningitis of H2D(b) KO mice was linked to the development o f a subdominant (in normal B6 mice) H2K(b)-restricted cytotoxic T lymphocyt e response. Mice expressing a restricted set of histocompatibility class I molecules should represent useful tools to evaluate the immunological poten tials of individual MHC class I molecules.