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.