Structure, assembly and intracellular transport of the T cell receptor for antigen.
The T cell receptor for antigen (TCR) is responsible for the recognition of antigen associated with the major histocompatibility complex (MHC). The TCR expressed on the surface of T cells is associated with an invariant structure, CD3. CD3 is assumed to be responsible for intracellular signaling following occupancy of the TCR by ligand. The TCR/CD3 complex consists of six different polypeptides, and represents a uniquely complex multisubunit assembly problem for the cell. The cell copes with this problem by regulating the intracellular assembly of the complex. Within the endoplasmic reticulum, the newly-synthesised chains assemble into the complete structure prior to transport to the cell surface. There are a series of different isoforms of the receptor involving differential use of the TCR heterodimer (alpha-beta or gamma-delta), zeta-family member, and CD3 gamma or delta chains. These are presumably linked to different TCR functions. Assembly of the TCR/CD3 complex competes with specific degradation of unassembled polypeptides. The fate of the receptor depends on the presence of subtle signals on individual chains which determine pairing and assembly or degradation. The T cell is thus able to select a completely assembled fully functional series of distinct TCR/CD3 complexes for expression at the cell surface.
Laboratory of Molecular Immunology, Dana Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115.
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Exley
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Terhorst
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Wileman
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D017252:CD3 Complex; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D018833:Chaperonins; D015536:Down-Regulation; D005796:Genes; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D018833:Chaperonins