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-Immunoreceptor Tyrosine-Based Activation Motif in Mature T Cell Function1
*
Division of Immunology,
Division of Cellular Biochemistry, and
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
At least four different CD3 polypeptide chains are contained within
the mature TCR complex, each encompassing one (CD3
, CD3
, and
CD3
) or three (CD3
) immunoreceptor tyrosine-based activation
motifs (ITAMs) within their cytoplasmic domains. Why so many ITAMs are
required is unresolved: it has been speculated that the different ITAMs
function in signal specification, but they may also serve in signal
amplification. Because the CD3 chains do not contribute unique
signaling functions to the TCR, and because the ITAMs of the
CD3- module alone can endow the TCR with normal signaling
capacity, it thus becomes important to examine how the CD3-, -,
and -ITAMs regulate TCR signaling. We here report on the role of the
CD3 chain and the CD3-ITAM in peripheral T cell activation and
differentiation to effector function. All T cell responses were reduced
or abrogated in T cells derived from CD3 null-mutant mice, probably
because of decreased expression levels of the mature TCR complex
lacking CD3. Consistent with this explanation, T cell responses
proceed undisturbed in the absence of a functional CD3-ITAM. Loss of
integrity of the CD3-ITAM only slightly impaired the regulation of
expression of activation markers, suggesting a quantitative
contribution of the CD3-ITAM in this process. Nevertheless, the
induction of an in vivo T cell response in influenza A virus-infected
CD3-ITAM-deficient mice proceeds normally. Therefore, if ITAMs can
function in signal specification, it is likely that either the CD3
and/or the CD3 chains endow the TCR with qualitatively unique
signaling functions.
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