Post-transcriptional regulation of MHC class II expression in human T cells.
Human T lymphocytes are among those cells which are cell surface class II- in the resting state, but can be induced to express class II following treatment with appropriate stimulators. Although resting T cells do not express detectable surface class II, cell surface class II can be detected on purified T cells as early as 30 min following stimulation with PHA and PMA, well before the initiation of DNA synthesis, and the percentage of positive cells gradually increases with time. One hypothesis explaining this very rapid surface expression of class II is that the genes can be regulated post-transcriptionally in T cells. To test this, we used nuclear run-on assays to measure the transcriptional rate of diverse class II genes in resting and activated T cells. Our results demonstrated that transcripts for DR, DP, and DQ could be detected in cells which were neither dividing nor transcribing mRNA for another marker of T cell activation, the IL-2 gene. Northern blot analysis demonstrated low to moderate steady-state levels of DR beta mRNA in these cells. Moreover, treatment of activated T cells with cycloheximide resulted in superinduction of class II for DR, DQ, and DP. These results suggest that resting T cells can transcribe mRNA for class II genes, but that they do not express the protein product on the cell surface in a detectable way until following activation. In addition, they suggest that there may be a protein factor which negatively influences class II levels in T cells. Thus, the regulation of class II in T cells is complex and involves post-transcriptional regulation, at least in part.
Caplen
H S
HS
Department of Medicine, Mt. Sinai School of Medicine, New York, New York 10029.
Salvadori
S
S
Gansbacher
B
B
Zier
K S
KS
D015152:Blotting, Northern; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic
D006681:HLA-D Antigens; D012333:RNA, Messenger; D003513:Cycloheximide