Structure/function analysis of the invariant subunits of the T cell antigen receptor.
The T cell antigen receptor (TCR) is a multimeric surface receptor on T cells responsible for recognizing MHC-restricted antigens and initiating the cellular immune response. The clonotypic nature of the TCR resides in the antigen binding TCR-alpha beta or TCR-gamma delta heterodimer. The CD3 complex of gamma, delta and epsilon and the zeta-family disulfide dimer comprise the invariant TCR chains. Assembly of the mature TCR complex requires specific subunit interactions, the detailed nature of which is becoming more evident. Surface targetting of the TCR appears dependent on a region of the zeta chain near its transmembrane domain. A functional role attributable to zeta residing in the cytoplasmic tail is the capacity to couple antigen stimulation to IL-2 secretion, likely through activation of a tyrosine kinase. Assignment of functional roles for the remaining CD3 chains is not as clear; the removal of the cytoplasmic tail of CD3-delta does not affect TCR-mediated IL-2 signalling. Mounting evidence indicates that the structural complexity of the TCR is further enhanced by the various zeta family disulfide dimer pairs that can associate with the other TCR chains. This subunit diversification may offer the possibility of multiple coupling pathways available to the TCR as it responds to foreign antigens in various contexts.
Frank
S J
SJ
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Engel
I
I
Rutledge
T M
TM
Letourneur
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology* / Q000648:ultrastructure; D017252:CD3 Complex; D003593:Cytoplasm / Q000648:ultrastructure; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D019000:Phosphotyrosine; D011948:Receptors, Antigen, T-Cell / Q000502:physiology* / Q000648:ultrastructure; D011961:Receptors, Fc / Q000737:chemistry; D017455:Receptors, IgE; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; C054979:antigen T cell receptor, zeta chain; D019000:Phosphotyrosine; D014443:Tyrosine