Thymic selection of cytotoxic T cells independent of CD8 alpha-Lck association.
The CD8 alpha cytoplasmic domain associates with p56lck, a nonreceptor protein-tyrosine kinase. The biological relevance of CD8 alpha-Lck association in T cell development was tested with transgenic mice generated to express a CD8 alpha molecule with two amino acid substitutions in its cytoplasmic domain, which abolishes the association of CD8 alpha with Lck. The CD8 alpha mutant was analyzed in a CD8-/- background and in the context of the transgenic 2C T cell receptor. The development and function of CD8+ T cells in these mice were apparently normal. Thus, CD8 alpha-Lck association is not necessary for positive selection, negative selection, or CD8-dependent cytotoxic function.
Howard Hughes Medical Institute, Department of Medicine, Genetics, and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.
I T
IT
Chan
A
A
Limmer
M C
MC
Louie
E D
ED
Bullock
W P
WP
Fung-Leung
T W
TW
Mak
D Y
DY
Loh
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005805:Genes, MHC Class I; D007959:Lymphocyte Culture Test, Mixed; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)