Evidence map›Paper›PMID 40073094›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2025

Quantitative detection of the HVEM-BTLA checkpoint receptor cis-complex in human lymphocytes.

Shane Atwell, Timothy C Cheung, Elaine M Conner, Carolyn Ho, Jiawen Huang, Erin L Harryman, Ricky Lieu, Stacie Lim, Wai W Lin, Diana I Ruiz and 2 more

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. MutantFrontiers in immunology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Shane AtwellBiotechnology Discovery Research, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, United States.ORCID 0000-0002-2578-2462
Timothy C CheungInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
Elaine M ConnerBiotechnology Discovery Research, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, United States.
Carolyn HoBiotechnology Discovery Research, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, United States.
Jiawen HuangInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
Erin L HarrymanInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
Ricky LieuBiotechnology Discovery Research, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, United States.
Stacie LimInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.ORCID 0009-0001-7972-8373
Wai W LinInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
Diana I RuizBiotechnology Discovery Research, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, United States.
Andrew C VendelImmunology Discovery Research, Eli Lilly and Company, Lilly Biotechnology Center, San Diego, CA, United States.ORCID 0009-0002-6466-348X
Carl F WareInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.ORCID 0000-0002-5006-418X

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
NCI NIH HHS P30 CA030199SBP-Lilly Collaborative Research RCA15-15SBP-Lilly Collaborative Research Agreement RCA15-15
6 · The paper itself

Abstract

The herpesvirus entry mediator (HVEM) (TNFRSF14) engagement of the checkpoint inhibitory receptor B and T lymphocyte attenuator (BTLA) limits immune responses of T and B lymphocytes. HVEM and BTLA form signaling complexes in trans and when coexpressed, complexes in cis, creating a unique immune checkpoint. The function of the HVEM-BTLA cis-complex is not well understood primarily due to a lack of reagents that specifically measure the HVEM-BTLA cis-complex. We describe here a method to generate antibodies to receptor-ligand complexes using fusion immunogens, in this case, a BTLA-HVEM fusion protein. We identified 2 closely related antibodies that specifically recognize the HVEM-BTLA complex on the cell surface. In experiments utilizing the anti-HVEM-BTLA complex-specific antibody together with subunit-specific BTLA monoclonal antibodies, we were able to determine the precise ratio of free to cis-complexed BTLA on subpopulations of human lymphocytes. This is the first direct quantification of the HVEM-BTLA cis-complex. The method described here should apply to the detection of other receptor-ligand complexes.

Indexed as

LymphocytesReceptors, ImmunologicReceptors, Tumor Necrosis Factor, Member 14Antibodies, MonoclonalHumansAntibodies, MonoclonalBTLA protein, humanReceptors, ImmunologicReceptors, Tumor Necrosis Factor, Member 14TNFRSF14 protein, humanB and T lymphocyte attenuatorcheckpoint inhibitory receptorHerpesvirus entry mediatorHVEM-BTLA complex specific antibodytarget and receptor occupancy

Identifiers

PMID40073094
PMCPMC12213244

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.