TY - JOUR
T1 - Developmental regulation of αβ T cell antigen receptor assembly in immature CD4+CD8+ thymocytes
AU - Kearse, Kelly P.
AU - Roberts, Joseph P.
AU - Wiest, David L.
AU - Singer, Alfred
PY - 1995/12
Y1 - 1995/12
N2 - Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ T cells. Recent evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development.
AB - Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ T cells. Recent evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development.
KW - Animals
KW - CD4 Antigens/analysis
KW - CD8 Antigens/analysis
KW - Humans
KW - Receptors, Antigen, T-Cell, alpha-beta/biosynthesis
KW - T-Lymphocyte Subsets/immunology
KW - Thymus Gland/cytology
UR - http://www.scopus.com/inward/record.url?scp=0029583776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-0029583776&partnerID=MN8TOARS
U2 - 10.1002/bies.950171209
DO - 10.1002/bies.950171209
M3 - Review article
C2 - 8634066
SN - 0265-9247
VL - 17
SP - 1049
EP - 1054
JO - BioEssays
JF - BioEssays
IS - 12
ER -