Abstract
We recently reported a novel autosomal recessive mouse mutation designated nackt (nkt). Homozygous mutant mice have diffuse alopecia and a marked reduction in the proportion of CD4+ T cells in the thymus and peripheral lymphoid tissues. Here we show that the CD4 T-cell deficiency is due to a defect in the thymic microenvironment rather than the hematopoietic compartment. Furthermore, we identified the molecular basis of the mutant phenotype by demonstrating that the nkt mutation represents a 118-bp deletion of the cathepsin L (Ctsl) gene which is required for degradation of the invariant chain, a critical chaperone for major histocompatibility complex class II molecules. This finding explains the similarities in skin and immune defects observed in nkt/nkt and Ctsl -/- mice. The data reported here provide further in vivo evidence that the lysosomal cysteine protease cathepsin L plays a critical role in CD4+ T-cell selection in the thymus.
Original language | English (US) |
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Pages (from-to) | 233-242 |
Number of pages | 10 |
Journal | Immunogenetics |
Volume | 53 |
Issue number | 3 |
DOIs | |
State | Published - 2001 |
Keywords
- CD4 deficiency
- Cathepsin L
- Hair loss mutation
- Laboratory mouse
- T-cell selection
ASJC Scopus subject areas
- Immunology
- Genetics