Peptide selectivity of killer cell immunoglobulin-like receptors differs with allotypic variation in HLA class I DOI Creative Commons
Philippa M. Saunders, Patricia T. Illing, Lachlan Coin

et al.

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Natural killer (NK) cell activation is regulated by immunoglobulin-like receptors (KIRs) that recognize human leukocyte antigen (HLA) class I molecules. While polymorphism in HLA can directly impact these interactions, the extent to which HLA-associated peptide repertoire modulates NK function less well understood. Therefore, requirements for recognition of 2 ligands, HLA-B*57:01 and HLA-A*24:02, share similar KIR3DL1 binding residues but differ their capacity inhibit cells were assessed. Immunopeptidome functional analyses endogenous peptides associated with each allotype showed both repertoires contained capable facilitating or impairing KIR3DL1-dependent target cells. distinct sequence features at positions 7 8 bound similarly impacted allotypes, remained a more potent ligand overall. In silico suggested most presented would facilitate engagement, whereas HLA-A*24:02 possessed fewer predicted support strong recognition. Nevertheless, exogenous addition highly permissive expressing could bolster KIR3DL1-mediated inhibition peptide-competent levels seen HLA-B*57:01. Together, data indicate allotypic differences KIR suggest have potential sense infection- transformation-induced perturbations, particularly when intrinsic KIR/HLA interactions are modest avidity.

Language: Английский

SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity DOI Creative Commons
Chihiro Motozono,

Mako Toyoda,

Jiří Zahradník

et al.

Cell Host & Microbe, Journal Year: 2021, Volume and Issue: 29(7), P. 1124 - 1136.e11

Published: June 15, 2021

Many SARS-CoV-2 variants with naturally acquired mutations have emerged. These can affect viral properties such as infectivity and immune resistance. Although the sensitivity of occurring to humoral immunity has been investigated, human leukocyte antigen (HLA)-restricted cellular remains largely unexplored. Here, we demonstrate that two recently emerging in receptor-binding domain spike protein, L452R (in B.1.427/429 B.1.617) Y453F B.1.1.298), confer escape from HLA-A24-restricted immunity. reinforce affinity toward host entry receptor ACE2. Notably, mutation increases stability, infectivity, fusogenicity, thereby promotes replication. data suggest HLA-restricted potentially affects evolution phenotypes a further threat pandemic is

Language: Английский

Citations

525
High-throughput and single-cell T cell receptor sequencing technologies DOI
Joy A. Pai, Ansuman T. Satpathy

Nature Methods, Journal Year: 2021, Volume and Issue: 18(8), P. 881 - 892

Published: July 19, 2021

Language: Английский

Citations

212
Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy DOI Creative Commons
Guo Luo, Aditya Ambati, Ling Lin

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(52)

Published: Dec. 12, 2018

Significance This work shows that the amidated terminal ends of secreted hypocretin (HCRT) peptides (HCRT NH2 ) are autoantigens in type 1 narcolepsy, an autoimmune disorder targeting HCRT neurons. The process is usually initiated by influenza A flu infections, and a particular piece hemagglutinin (HA) protein pandemic 2009 H1N1 strain was identified as likely trigger. HA epitope has homology with T cells cross-reactive to both epitopes involved molecular mimicry. Genes associated narcolepsy mark HLA heterodimer (DQ0602) presentation these antigens modulate expression specific cell receptor segments (TRAJ24 TRBV4-2) recognition antigens, suggesting causality.

Language: Английский

Citations

175
NetTCR-2.0 enables accurate prediction of TCR-peptide binding by using paired TCRα and β sequence data DOI Creative Commons

Alessandro Montemurro,

Viktoria Schuster, Helle Rus Povlsen

et al.

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: Sept. 10, 2021

Abstract Prediction of T-cell receptor (TCR) interactions with MHC-peptide complexes remains highly challenging. This challenge is primarily due to three dominant factors: data accuracy, scarceness, and problem complexity. Here, we showcase that “shallow” convolutional neural network (CNN) architectures are adequate deal the complexity imposed by length variations TCRs. We demonstrate current public bulk CDR3β-pMHC binding overall low quality development accurate prediction models contingent on paired α/β TCR sequence corresponding at least 150 distinct pairs for each investigated pMHC. In comparison, trained CDR3α or CDR3β alone demonstrated a variable pMHC specific relative performance drop. Together these findings support specificity predictable given availability sufficient data. NetTCR-2.0 publicly available https://services.healthtech.dtu.dk/service.php?NetTCR-2.0 .

Language: Английский

Citations

171
Emerging phagocytosis checkpoints in cancer immunotherapy DOI Creative Commons
Yue Liu, Yanjin Wang, Yanrong Yang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 7, 2023

Abstract Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered cells, has revolutionized oncology landscape as it utilizes patients’ own systems in combating cancer cells. cells escape surveillance by hijacking corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such CD47, CD24, MHC-I, PD-L1, STC-1 GD2, have emerged essential checkpoints for immunotherapy functioning “don’t eat me” signals or interacting with “eat to suppress responses. link innate immunity adaptive immunotherapy. Genetic ablation these phagocytosis well blockade their signaling pathways, robustly augments reduces tumor size. Among all CD47 is most thoroughly studied a rising star among targets treatment. CD47-targeting antibodies inhibitors been investigated various preclinical clinical trials. However, anemia thrombocytopenia appear be formidable challenges since ubiquitously expressed on erythrocytes. Here, we review reported discussing mechanisms functions highlight progress targeting discuss potential solutions smooth way combination immunotherapeutic strategies that involve both

Language: Английский

Citations

157
Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future DOI Creative Commons
José Saura‐Esteller,

Milon de Jong,

Lisa A. King

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 16, 2022

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel T-cell-based immunotherapies, primarily focusing on the two major T-cell subtypes that infiltrate tumors ( i.e. Vδ1 Vδ2), are being developed. The subset is enriched in tissues contains both as well regulatory with tumor-promoting potential. Vδ2 T-cells, contrast, circulation consist large, relatively homogeneous, pro-inflammatory subset. Healthy individuals typically harbor order 50-500 million Vγ9Vδ2 peripheral blood alone (1-10% total CD3 + population), can rapidly expand upon stimulation. receptor senses intracellular phosphorylated metabolites, accumulate result mevalonate pathway dysregulation or pharmaceutical intervention. Early clinical studies investigating therapeutic potential were based either ex vivo expansion adoptive transfer their systemic activation aminobisphosphonates synthetic phosphoantigens, combined low dose IL-2. Immune-related adverse events (irAE) generally \mild, but efficacy these approaches provided overall limited benefit. In recent years, critical advances have renewed excitement Here, we review strategies discuss prospects those currently evaluated patients future therapies might arise from current pre-clinical results.

Language: Английский

Citations

133
Contribution of T Cell Receptor Alpha and Beta CDR3, MHC Typing, V and J Genes to Peptide Binding Prediction DOI Creative Commons

Ido Springer,

Nili Tickotsky, Yoram Louzoun

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 26, 2021

Predicting the binding specificity of T Cell Receptors (TCR) to MHC-peptide complexes (pMHCs) is essential for development repertoire-based biomarkers. This affinity may be affected by different components TCR, peptide, and MHC allele. Historically, main element used in TCR-peptide prediction was Complementarity Determining Region 3 (CDR3) beta chain. However, recently contribution other components, such as alpha chain V gene CDRs has been suggested. We use a highly accurate novel deep learning-based predictor assess each component binding.We have previously developed ERGO-I (pEptide tcR matchinG predictiOn), sequence-based T-cell receptor (TCR)-peptide that employs natural language processing (NLP) -based methods. improved it create ERGO-II adding CDR3 segment, typing, J genes, cell type (CD4+ or CD8+) predictor. then estimate prediction.ERGO-II provides first time high accuracy unseen peptides. For most tested peptides all measures accuracy, from sequence, followed chain, order. The allele least contributing component. accessible webserver at http://tcr2.cs.biu.ac.il/ standalone code https://github.com/IdoSpringer/ERGO-II.

Language: Английский

Citations

117
New immune cell engagers for cancer immunotherapy DOI

Aurore Fenis,

Olivier Demaria, Laurent Gauthier

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(7), P. 471 - 486

Published: Jan. 25, 2024

Language: Английский

Citations

76
Novel insights into the immune response to bacterial T cell superantigens DOI
Stephen W. Tuffs, Karine Dufresne, Aanchal Rishi

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(6), P. 417 - 434

Published: Jan. 15, 2024

Language: Английский

Citations

20
Using T Cell Receptor Repertoires to Understand the Principles of Adaptive Immune Recognition DOI Open Access
Philip Bradley, Paul G. Thomas

Annual Review of Immunology, Journal Year: 2019, Volume and Issue: 37(1), P. 547 - 570

Published: Jan. 30, 2019

Adaptive immune recognition is mediated by antigen receptors on B and T cells generated somatic recombination during lineage development. The high level of diversity resulting from this process posed technical limitations that previously limited the comprehensive analysis adaptive recognition. Advances over last ten years have produced data approaches allowing insights into how develop, evolutionary signatures selection, features cell mediate epitope-specific binding activation. size complexity these necessitated generation novel computational analytical approaches, which are transforming immunology conducted. Here we review development application biological, theoretical, methods for understanding discuss potential improved models receptor:antigen interactions.

Language: Английский

Citations

135