The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Burshtyn, Deborah N.; Morcos, Chris

doi:10.4049/jimmunol.1501937

Cited by 36 publications

(40 citation statements)

References 71 publications

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“…1B, Supplemental Table I). In addition, LILRB1, an ITIM-containing inhibitory receptor that signals downstream of interactions with HLA-G and several classical MHC class I alleles (28), was also found to be highly expressed by the T EMRA and T EM populations (Fig. 1B, Supplemental Table I), with preferential expression in T EMRA (Fig.…”

Section: Lilrb1-expressing Effector Cd8 + T Cells Can Efficiently Medmentioning

confidence: 97%

LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells

Kim

Han

Driver

et al. 2019

The Journal of Immunology

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Elicitation of tumor cell killing by CD8+ T cells is an effective therapeutic approach for cancer. In addition to using immune checkpoint blockade to reinvigorate existing but unresponsive tumor-specific T cells, alternative therapeutic approaches have been developed, including stimulation of polyclonal T cell cytolytic activity against tumors using bispecific T cell engager (BiTE) molecules that simultaneously engage the TCR complex and a tumor-associated Ag. BiTE molecules are efficacious against hematologic tumors and are currently being explored as an immunotherapy for solid tumors. To understand mechanisms regulating BiTE molecule–mediated CD8+ T cell activity against solid tumors, we sought to define human CD8+ T cell populations that efficiently respond to BiTE molecule stimulation and identify factors regulating their cytolytic activity. We find that human CD45RA+CCR7− CD8+ T cells are highly responsive to BiTE molecule stimulation, are enriched in genes associated with cytolytic effector function, and express multiple unique inhibitory receptors, including leukocyte Ig-like receptor B1 (LILRB1). LILRB1 and programmed cell death protein 1 (PD1) were found to be expressed by distinct CD8+ T cell populations, suggesting different roles in regulating the antitumor response. Engaging LILRB1 with its ligand HLA-G on tumor cells significantly inhibited BiTE molecule–induced CD8+ T cell activation. Blockades of LILRB1 and PD1 induced greater CD8+ T cell activation than either treatment alone. Together, our data suggest that LILRB1 functions as a negative regulator of human CD8+ effector T cells and that blocking LILRB1 represents a unique strategy to enhance BiTE molecule therapeutic activity against solid tumors.

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Section: Lilrb1-expressing Effector Cd8 + T Cells Can Efficiently Medmentioning

confidence: 97%

LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells

Kim

Han

Driver

et al. 2019

The Journal of Immunology

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“…Interestingly, some of the human inhibitory leukocyte immunoglobulin-like receptors have been shown to interact with the gene CD1d [30], which was only seen as being upregulated in the MLV vs. KV and MLV vs. NON comparisons.…”

Section: Overexpression Of Key Genes Related To Promoting Adaptive Immentioning

confidence: 99%

Transcriptomic analysis among sub-clinically ill cattle following Bovine Respiratory Disease vaccine protocol and challenge with Bovine Viral Diarrhea Virus

Fleming¹,

Herring²,

Miller³

et al. 2019

Preprint

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Background: Bovine viral diarrhea (BVD) is a widespread immunosuppressive disease of cattle. Infection with bovine viral diarrhea virus (BVDV) can also be sub-clinical and persistent in herds, leading to high economic impact to cattle producers. Complicating this is BVD’s ability to predispose cattle to bovine respiratory disease (BRD) complex. Although many producers vaccinate for BRD to help protect herds from this predisposition, there are gaps in the knowledge of differences between the protection afforded by modified live (MLV) or killed (KV) vaccines, and the level of cross-protection they offer to BVDV. These knowledge gaps affect the economic impact of BVDV because, with more information on vaccine efficacy, cattle producers could possibly reduce treatment costs and disease spread. The study objective was to determine the level of BRD vaccine cross-protection by examining the underlying differential gene expression response to a sub-clinical BVDV challenge in Nellore-Angus cattle. Results: Statistical analysis of clinical data showed that MLV had lower BVDVa, BVDV2, and BVDVb antibody titers (p < 0.001) compared to the KV vaccine. The three treatment groups (no vaccine (NON), KV, MLV; n = 5 per group) were also compared by RNA-seq analysis of buffy coats from cattle at 14 dpi. The BRD KV group displayed a higher antibody (AB) response, however transcriptomic analysis showed that the KV group still showed high innate gene expression at 14 dpi. The MLV showed displayed a higher number of adaptive and cell-mediated immune response genes being differentially expressed in reaction to challenge at 14 dpi. Analysis also showed the difference in vaccine cross-protection involved evidence of complement activation as part of the MLV bolstered immune response. Lack of detection of complement activation in the KV group could explain the higher titers, while complement activation in the MLV group could lead to less AB response due to better cell-mediated response. Upregulation of MHC molecules and T-cell related gene expression was also observed within the MLV group only. Conclusions: Although both vaccines provide some level of cross-protection over non-vaccinated animals, the results point to MLV producing cross-protection that extends the adaptive immune response to BVDV.

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“…The variety of shared ligands for the paired receptors is impressive. Paired receptors recognise everything from proteins to sugars, to lipids, to nucleic acids ( [31] and Table 1). This vast diversity of potential ligands indicates that they might be involved in a large number of immune responses and clinical situations, many of which remain to be discovered.…”

Section: Ligands For the Paired Receptorsmentioning

confidence: 99%

Inhibitory and Coactivating Receptors Recognising the Same Ligand: Immune Homeostasis Exploited by Pathogens and Tumours

Levi‐Schaffer

Mandelboim

2018

Trends in Immunology

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Coactivating and inhibitory receptors that share at least one ligand interact with a wide variety of ligands, indicating their importance in a range of situations. Here, we discuss principles of mainly human paired receptor function and ligand recognition, and possible therapeutic implications of targeting these receptors in cancer, autoimmune diseases, and allergy. We summarise and emphasise the idea that these receptors, which have evolved in part in response to pathogen pressure, fine-tune the immune response, preserve homeostasis, and that pathogens and tumours use the dominance of the inhibitory receptors over the coactivating receptors to avoid immune elimination. Finally, we discuss the options of using paired receptors and their ligand for immune cell education and therapy.

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The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Cited by 36 publications

References 71 publications

LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells

LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells

Transcriptomic analysis among sub-clinically ill cattle following Bovine Respiratory Disease vaccine protocol and challenge with Bovine Viral Diarrhea Virus

Inhibitory and Coactivating Receptors Recognising the Same Ligand: Immune Homeostasis Exploited by Pathogens and Tumours

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