An atlas of natural killer cell receptor expression on healthy donor T and NK lymphocytes
Bibliographic record
Abstract
ABSTRACT Human T cells and natural killer (NK) cells exhibit variegated co-expression of germlineencoded receptors, which diversifies their effector functions. CD8+ T cell expression of receptors more typically associated with NK cells has been noted, but a systematic analysis of their distribution has not been described. Here, we comprehensively measured human NK cells and T cells’ expression of NK cell-associated receptors to define their co-expression and patterns associated with donor sex, maturation, and activation. To assess the activating and inhibitory receptor repertoire of human T cells and NK cells, we developed a 25-colour flow cytometry panel that included channels based on receptor functions. Since NK cell function is known to be driven by interactions with HLA supergroups (KIR ligands), we stratified donors based on KIR-HLA allelic combinations. NK and CD8+ T cell phenotypes and responsiveness were assessed at rest, and in response to the missing self target cell line, K562. We find that NK cells universally express CD45RA, CD161, and the inhibitory receptors TIGIT/TIM3/LAG3. On CD56 dim CD16 high NK cells (those most aligned with missing self reactivity, CD161, CD45RA, natural cytotoxicity receptors (NCRs), and TIGIT/TIM3/LAG3 were most frequently expressed. Not all educated NK cells respond to missing self-targets; those that did exhibited high expression of NCRs, NKG2C, IL-7R/IL-18Ra, and TIGIT/TIM3/LAG3, and lower expression of DNAM-1 and CCR7, in addition to the KIR molecules that defined their status as educated. We note that up to 50% of NK cells express CD8, and this population co-expressed CD16, NCRs, and KIR, and exhibited greater cytotoxicity than the CD8-NK cell population. Among CD8 + T cells, acquisition of NK cell-associated receptors was increased as they progressed through differentiation states: effector memory and terminally-differentiated CD8 + T cells exhibiting higher expression of NKG2A, KIR, and CD16. Taken together, the variability of receptor expression patterns highlights the diversity of lymphocyte populations and suggests shared features among the cytotoxic lymphocytes.
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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 | 0.001 | 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) | 0.003 | 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".