Lymphocyte Development in Mice Deficient for MHC Class I Expression

Abstract

The role of MHC Class I molecules in recognition of antigens by CD8⁺ T cells is well established, as is their role in the development of CD8⁺ T cells. The study of animals unable to normally express class I molecules provides an approach to learn about the role of class I molecules not only in CD8⁺ T cell development, but possibly in other cell types as well. This can be accomplished by analysis of mice mutant for the light chain of class I MHC, β2-microglobulin, which is necessary for normal functional cell surface expression of class I molecules. Such mice were produced in two laboratories by substitution of the normal β2-microglobulin gene for a mutant one, by homologous recombination embryonic stem cells, which were allowed to repopulate the germ line in chimeric mice ^{1, 2, 3, 4}. In previous studies, we and others reported that mice homozygous for the mutant β2-m gene have severely diminished cell surface expression of MHC-I molecules, and are severely deficient in the production of functional, mature CD8⁺CD4^- T cells ^2,4. In this article, we summarize our recent work on the role of MHC-I molecules in development of CD8⁺ T cells, CD4-CD8-∝β⁺ T cells, and γδ⁺ T cells. In addition the role of MHC-I molecules in the development of natural killer (NK) cells is discussed.