CD43 polarization in unprimed T cells can be dissociated from raft coalescence by inhibition of HMG CoA reductase.
Movement of T-lymphocyte cell surface CD43 is associated with both antigen activation of T-cell clones and chemokine induction of T-lymphocyte motility. Here, we demonstrate that CD43 movement away from the site of T-cell receptor ligation occurs in unprimed CD4(+) T cells as well as T-cell clones. The T-cell receptor (TCR)-dependent movement of CD43 in unprimed T cells is associated with a polarized morphology and CD43 accumulation at the uropods of the cells, unlike that reported for primed T cells. The polarization of CD43 has a requirement for Src kinases and occurs in conjunction with lipid raft coalescence. Thymocytes and T-cell hybridomas, cells that have altered responses to TCR activation and lack lipid raft coalescence, do not polarize CD43 as readily as unprimed T cells. The movement of CD43 depends on the cholesterol biosynthetic pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. Blockade of this enzyme can specifically prevent CD43 redistribution without affecting cell shape polarization. The likely mechanism of this alteration in CD43 redistribution is through decreased protein prenylation because the cholesterol-dependent lipid rafts still coalesce on activation. These findings suggest that the polarization of cell shape, lipid raft coalescence, and CD43 redistribution on T-cell activation have signaling pathway distinctions. Dissecting out the relationships between various stages of molecular redistribution and lymphocyte activation may facilitate fine-tuning of immunologic responses.
Gubina
Elena
E
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bldg. 29B-3NN08, 29 Lincoln Drive, Bethesda, MD 20892, USA.
Chen
Trina
T
Zhang
Lei
L
Lizzio
Elaine F
EF
Kozlowski
Steven
S
D000818:Animals; D015703:Antigens, CD; D016764:Cell Polarity / Q000276:immunology; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051917:Leukosialin; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D021962:Membrane Microdomains / Q000502:physiology*; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D011743:Pyrimidines / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
C412373:AG 1879; D015703:Antigens, CD; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051917:Leukosialin; D011743:Pyrimidines; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C012258:mevastatin; C015367:mevalonolactone; D008148:Lovastatin; D019061:src-Family Kinases; D008798:Mevalonic Acid