The cytoplasmic domain of CD8 beta regulates Lck kinase activation and CD8 T cell development.
Previous studies have shown that CD8 beta plays a role in both enhancing CD8 alpha-associated Lck kinase activity and promoting the development of CD8-lineage T cells. To examine the role of this enhancement in the maturation of CD8-lineage cells, we assessed CD8 alpha-associated Lck kinase activity in both T cell hybridomas and thymocytes of mice expressing CD8 beta mutations known to impair CD8 T cell development. Lack of CD8 beta expression or expression of a cytoplasmic domain-deleted CD8 beta resulted in a severalfold reduction in CD8 alpha-associated Lck kinase activity compared with that observed with cells expressing wild-type CD8 beta chain. This analysis indicated a critical role for the cytoplasmic domain of CD8 beta in the regulation of CD8 alpha-associated Lck activity. Decreased CD8 alpha-associated Lck activity observed with the various CD8 beta mutations also correlated with diminished in vivo cellular tyrosine phosphorylation. In addition, analysis of CD8 beta mutant mice (CD8 beta-/- or cytoplasmic domain-deleted CD8 beta transgenic) indicated that the degree of reduction in CD8 alpha-associated Lck activity associated with each mutation correlated with the severity of developmental impairment. These results support the importance of CD8 beta-mediated enhancement of CD8 alpha-associated Lck kinase activity in the differentiation of CD8 single-positive thymocytes.
Irie
H Y
HY
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Mong
M S
MS
Itano
A
A
Crooks
M E
ME
Littman
D R
DR
Burakoff
S J
SJ
Robey
E
E
D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D005822:Genetic Vectors / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007424:Intracellular Fluid / Q000201:enzymology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion / Q000276:immunology; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
D016827:CD8 Antigens; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)