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Piecing together the family portrait of TCR ‐ CD 3 complexes
Author(s) -
Kuhns Michael S.,
Badgandi Hemant B.
Publication year - 2012
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12000
Subject(s) - genetics , biology
Summary The pre‐T‐cell receptor ( TCR )‐, αβ TCR ‐, and γδ TCR ‐ CD 3 complexes are members of a family of modular biosensors that are responsible for driving T‐cell development, activation, and effector functions. They inform essential checkpoint decisions by relaying key information from their ligand‐binding modules ( TCR s) to their signaling modules ( CD 3γε + CD 3δε and CD 3ζζ) and on to the intracellular signaling apparatus. Their actions shape the T‐cell repertoire, as well as T‐cell‐mediated immunity; yet, the mechanisms that underlie their activity remain an enigma. As with any molecular machine, understanding how they function depends upon understanding how their parts fit and work together. In the 30 years since the initial biochemical and genetic characterizations of the αβ TCR , the structure and function of the individual components of these family members have been extensively characterized. Cumulatively, this information has allowed us to piece together a portrait of the αβ TCR ‐ CD 3 complex and outline the form of the remaining family members. Here we review the known structural and functional characteristics of the components of these TCR ‐ CD 3 complex family members. We then discuss how these data have informed our understanding of the architecture of the αβ TCR ‐ CD 3 complex as well as their implications for the other family members. The intent is to provide a framework for considering: (i) how these thematically similar complexes diverge to execute their specific functions and (ii) how our knowledge of the form and function of these distinct family members can cross‐inform our understanding of the other family members.