CD3 delta deficiency arrests development of the alpha beta but not the gamma delta T cell lineage.
The CD3 complex found associated with the T cell receptor (TCR) is essential for signal transduction following TCR engagement. During T cell development, TCR-mediated signalling promotes the transition from one developmental stage to the next and controls whether a thymocyte undergoes positive or negative selection. The roles of particular CD3 components in these events remain unclear. Indeed, it is unknown whether they have specialized or overlapping roles. However, the multiplicity of CD3 components and their evolutionary conservation suggest that they serve distinct functions. Here the developmental requirement for the CD3 delta chain is analyzed by generating a mouse line specifically lacking this component (delta-/- mice). Strikingly, CD3 delta is shown to be differentially required during development. In particular, CD3 delta is not needed for steps in development mediated by pre-TCR or gamma delta TCR, but is required for further development of thymocytes expressing alpha beta TCR. Absence of CD3 delta specifically blocks the thymic selection processes that mediate the transition from the double-positive to single-positive stages of development.
Dave
V P
VP
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Cao
Z
Z
Browne
C
C
Alarcon
B
B
Fernandez-Miguel
G
G
Lafaille
J
J
de la Hera
A
A
Tonegawa
S
S
Kappes
D J
DJ
D000818:Animals; D017252:CD3 Complex / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta