BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1

Watanabe, Norihiko; Gavrieli, Maya; Šedý, John; Yang, Jianfei; Fallarino, Francesca; Loftin, Susan K.; Hurchla, Michelle A.; Zimmerman, Natalie; Sim, Julia; Zang, Xingxing; Murphy, Theresa L.; Russell, John H.; Allison, James P.; Murphy, Kenneth M.

doi:10.1038/ni944

Cited by 766 publications

(964 citation statements)

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“…Soon after, a manuscript reporting a mouse knockout of the same gene with an immune response phenotype was submitted by another group that had discovered the gene independently. 71 IRIS genes can also be used as cell markers in the analysis of microarray experiments. For example, tumor vs normal tissue analysis may benefit from recognition of genes involved in the immune response as opposed to carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

Abbas¹,

Baldwin²,

Ma³

et al. 2005

Genes Immun

360

356

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Immune cell-specific expression is one indication of the importance of a gene's role in the immune response. We have compiled a compendium of microarray expression data for virtually all human genes from six key immune cell types and their activated and differentiated states. Immune Response In Silico (IRIS) is a collection of genes that have been selected for specific expression in immune cells. The expression pattern of IRIS genes recapitulates the phylogeny of immune cells in terms of the lineages of their differentiation. Gene Ontology assignments for IRIS genes reveal significant involvement in inflammation and immunity. Genes encoding CD antigens, cytokines, integrins and many other gene families playing key roles in the immune response are highly represented. IRIS also includes proteins of unknown function and expressed sequence tags that may not represent genes. The predicted cellular localization of IRIS proteins is evenly distributed between cell surface and intracellular compartments, indicating that immune specificity is important at many points in the signaling pathways of the immune response. IRIS provides a resource for further investigation into the function of the immune system and immune diseases.

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Section: Discussionmentioning

confidence: 99%

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

Abbas¹,

Baldwin²,

Ma³

et al. 2005

Genes Immun

360

356

View full text Add to dashboard Cite

show abstract

“…B- and T-lymphocyte attenuator (BTLA) is another co-inhibitory receptor whose expression is induced during activation of T cells, leading to inhibition of human CD8 + cancer-specific T cells. 12 Like PD-1 and CTLA-4, BTLA interacts with a B7 homolog, B7H4, but unlike PD-1 and CTLA-4, BTLA displays T cell inhibition via interaction with tumor necrosis family receptors (TNF-R), not just the B7 family of cell surface receptors.…”

Section: Introductionmentioning

confidence: 99%

Massive parallel screening of phage libraries for the generation of repertoires of human immunomodulatory monoclonal antibodies

Sasso

D’Avino

Passariello

et al. 2018

mAbs

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Immune checkpoints are emerging as novel targets for cancer therapy, and antibodies against them have shown remarkable clinical efficacy with potential for combination treatments to achieve high therapeutic index. This work aims at providing a novel approach for the generation of several novel human immunomodulatory antibodies capable of binding their targets in their native conformation and useful for therapeutic applications.We performed a massive parallel screening of phage libraries by using for the first time activated human lymphocytes to generate large collections of single-chain variable fragments (scFvs) against 10 different immune checkpoints: LAG-3, PD-L1, PD-1, TIM3, BTLA, TIGIT, OX40, 4-1BB, CD27 and ICOS. By next-generation sequencing and bioinformatics analysis we ranked individual scFvs in each collection and identified those with the highest level of enrichment.As a proof of concept of the quality/potency of the binders identified by this approach, human IgGs from three of these collections (i.e., PD-1, PD-L1 and LAG-3) were generated and shown to have comparable or better binding affinity and biological activity than the clinically validated anti-PD-1 mAb nivolumab.The repertoires generated in this work represent a convenient source of agonistic or antagonistic antibodies against the ‘Checkpoint Immunome’ for preclinical screening and clinical implementation of optimized treatments.

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“…Additionally, SHP-2 can be co-precipitated with the inhibitory coreceptor CTLA-4 (CD152) and CD3-f, which has led to the hypothesis that SHP-2 mediates inhibitory signals from CTLA-4 [22][23][24][25]. Furthermore, other inhibitory molecules, such as PD-1 and BTLA, containing the canonical ITIM as well as ITSM motifs were shown to recruit SHP-2 in a phosphorylation-dependent manner [26,27]. Yet, a direct role of SHP-2 in their negative signaling cascade has not been shown.…”

Section: Introductionmentioning

confidence: 99%

The tyrosine phosphatase SHP‐2 regulates differentiation and apoptosis of individual primary T lymphocytes

Hoff

Brunner‐Weinzierl

2007

Eur J Immunol

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Although phosphatases are key players of intracellular processes, not much is known about the phosphatase SHP-2 during T cell differentiation. Here we show that ectopic over-expression of SHP-2 in primary T helper cells directly reduced the frequency of individual lymphocytes expressing pro-inflammatory cytokines after antigen-specific stimulation by a mechanism impairing activation of protein kinase C. In addition we demonstrate that SHP-2 mediates enhanced migration upon CXCR4 signaling in a G-protein-dependent manner. Most strikingly, SHP-2 mediated a dramatic increase in apoptosis by highly enhanced activation of caspases. Co-immunoprecipitations of SHP-2 and c-Cbl from primary T helper cells demonstrated that SHP-2 strongly interacts with the ubiquitin ligase c-Cbl, indicating that c-Cbl could mediate the negative signals of SHP-2. Our results show that SHP-2 signal transduction regulates central checkpoints of T cell differentiation by the activation of distinct signaling cascades.

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BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1

Cited by 766 publications

References 50 publications

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

Massive parallel screening of phage libraries for the generation of repertoires of human immunomodulatory monoclonal antibodies

The tyrosine phosphatase SHP‐2 regulates differentiation and apoptosis of individual primary T lymphocytes

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