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BRIEF DEFINITIVE REPORT |
T cell receptor explains different phenotypes of CD3 and CD3 immunodeficiencies
CORRESPONDENCE Wolfgang Schamel: schamel{at}immunbio.mpg.de
The
T cell receptor for antigen (TCR) comprises the clonotypic TCR, the CD3 (CD3
and/or CD3), and the 
dimers. T cells do not develop in CD3-deficient mice, whereas human patients lacking CD3 have abundant peripheral blood T cells expressing high TCR levels. In an attempt to identify the molecular basis for these discordant phenotypes, we determined the stoichiometries of mouse and human TCRs using blue native polyacrylamide gel electrophoresis and anti-TCR–specific antibodies. The TCR isolated in digitonin from primary and cultured human T cells includes CD3, with a TCRCD322 stoichiometry. In CD3-deficient patients, this may allow substitution of CD3 by the CD3 chain and thereby support T cell development. In contrast, the mouse TCR does not incorporate CD3 and has a TCRCD3222 stoichiometry. CD3-deficient mice exhibit a block in T cell development. A human, but not a mouse, CD3 transgene rescues T cell development in mice lacking both mouse CD3 and CD3 chains. This suggests important structural and/or functional differences between human and mouse CD3 chains during T cell development. Collectively, our results indicate that the different T cell phenotypes between CD3-deficient humans and mice can be explained by differences in their TCR composition.
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T cell receptor explains different phenotypes of CD3 and CD3 immunodeficiencies
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