Structural basis of clade‐specific HIV‐1 neutralization by humanized anti‐V3 monoclonal antibody KD‐247
Bibliographic record
Abstract
Humanized monoclonal antibody KD‐247 targets the Gly 312 ‐Pro 313 ‐Gly 314 ‐Arg 315 arch of the third hypervariable (V3) loop of the HIV‐1 surface glycoprotein. It potently neutralizes many HIV‐1 clade B isolates, but not of other clades. To understand the molecular basis of this specificity, we solved a high‐resolution (1.55 Å) crystal structure of the KD‐247 antigen binding fragment and examined the potential interactions with various V3 loop targets. Unlike most antibodies, KD‐247 appears to interact with its target primarily through light chain residues. Several of these interactions involve Arg 315 of the V3 loop. To evaluate the role of light chain residues in the recognition of the V3 loop, we generated 20 variants of KD‐247 single‐chain variable fragments with mutations in the antigen‐binding site. Purified proteins were assessed for V3 loop binding using Alpha‐Screen technology and for HIV‐1 neutralization. Our data revealed that recognition of the clade‐specificity defining residue Arg 315 of the V3 loop is based on a network of interactions that involve Tyr L32 , Tyr L92 , and Asn L27d that directly interact with Arg 315 , thus elucidating the molecular interactions of KD‐247 with its V3 loop target—Kirby, K. A., Ong, Y. T., Hachiya, A., Laughlin, T. G., Chiang, L. A., Pan, Y., Moran, J. L., Marchand, B., Singh, K., Gallazzi, F., Quinn, T. P., Yoshimura, K., Murakami, T., Matsushita, S., Sarafianos, S. G., Structural basis of clade‐specific HIV‐1 neutralization by humanized anti‐V3 monoclonal antibody KD‐247. FASEB J. 29, 70–80 (2015). www.fasebj.org
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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 | 0.000 |
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".