The N-Terminal Region of HIV-1 Tat Protein Binds CD127 in Human CD8 T Cells to Target the Receptor for Down Regulation Through Tat's Basic Region
Bibliographic record
Abstract
We have previously shown that soluble HIV-1 Tat protein down regulates surface expression of the interleukin (IL)-7 receptor alpha-chain (CD127) on human CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. Once taken up by CD8 T cells, Tat translocates to the inner leaflet of the plasma membrane where it interacts with the cytoplasmic tail of CD127 inducing receptor internalization and degradation by the proteasome. Here we characterized the regions of Tat required to interact with CD127 and induce receptor down regulation from the cell surface. To do this, a series of histidine-tagged Tat deletion mutants were generated and expressed as purified soluble protein, or cloned into a DNA expression vector and transfected into primary human CD8 T cells and a CD127 expressing Jurkat cell line. Protein-protein interactions were assessed by co-immunoprecipitation. Substitution of the first 10 Nterminal residues or deletion of residues 17-21 prevented Tat from interacting with and down regulating CD127 from the cell surface. Deletion of the basic region also prevented Tat from down regulating CD127 but did not prevent Tat from binding to the receptor. Notably, an endogenously expressed Tat variant lacking the basic region caused an accumulation of CD127 at the cell surface. We propose a model where Tat interacts with CD127 via its N-terminal region and recruits cellular factors via its basic region to down regulate CD127 from the cell surface.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".