Immunology letters最新文献

Alterations in Chemokine Receptor-Ligand Interactions and Costimulatory Molecules in DC-NK Crosstalk: A Novel Therapeutic Approach for Pemphigus Vulgaris. 趋化因子受体-配体相互作用和DC-NK串扰中共刺激分子的改变：一种治疗寻常型天疱疮的新方法。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-27 DOI: 10.1016/j.imlet.2025.107055

Vishakha Hooda, Divya Sharma, Ashu Singh, Dayasagar Das, Somesh Gupta, Sudheer Arava, Alpana Sharma

{"title":"Alterations in Chemokine Receptor-Ligand Interactions and Costimulatory Molecules in DC-NK Crosstalk: A Novel Therapeutic Approach for Pemphigus Vulgaris.","authors":"Vishakha Hooda, Divya Sharma, Ashu Singh, Dayasagar Das, Somesh Gupta, Sudheer Arava, Alpana Sharma","doi":"10.1016/j.imlet.2025.107055","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107055","url":null,"abstract":"<p><p>Innate immune cells, particularly natural killer (NK) cells and dendritic cells (DCs), play a crucial role in the immunopathogenesis of Pemphigus Vulgaris (PV), an autoimmune blistering disorder. Dysregulation of these innate cells can lead to significant consequences in the adaptive immune response, contributing to disease progression. This study investigates the crosstalk between NK cells and DCs as a potential therapeutic target for PV. Our findings reveal an increased frequency of DCs (mDCs and pDCs) and NK cells (CD56<sup>dim</sup> and CD56<sup>bright</sup>) in the peripheral circulation of PV patients. NK cells exhibited elevated granzyme activity and IFNγ production, while DCs displayed enhanced phagocytic capabilities. In vitro, we observed upregulated mRNA expression of potentially interacting co-stimulatory markers (CD40 and CD80) and chemokines (CXCL10 and CXCL8) in DCs, alongside increased expression of their corresponding receptors (CD40L, CD80L, CXCR3, and CXCR1) on NK cells. Lesional tissues from PV patients also showed heightened expression of these receptor-ligand pairs. Co-culture experiments further demonstrated increased granzyme activity in NK cells and enhanced phagocytosis in DCs, however, blocking of CXCR3 resulted in decreased granzyme activity, suggesting a functional modulation through their interaction. These findings highlight the significant role of NK-DC crosstalk in PV pathogenesis and suggest that targeting this interaction could offer a novel therapeutic strategy to modulate immune responses in PV, offering the potential for more effective treatment approaches.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107055"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reduced CD37 expression in B cell subsets after stimulation and its clinical relevance in primary Sjögren's syndrome 刺激后B细胞亚群CD37表达降低及其与原发性Sjögren综合征的临床相关性

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-20 DOI: 10.1016/j.imlet.2025.107054

Zhonghui Zhang , Jie Chen , Ziqi Xiong , Weijie Lin , Bohao Yang , Zhiwei Zong , Bing Shen , Hanxi Luo , Chen Liu

{"title":"Reduced CD37 expression in B cell subsets after stimulation and its clinical relevance in primary Sjögren's syndrome","authors":"Zhonghui Zhang , Jie Chen , Ziqi Xiong , Weijie Lin , Bohao Yang , Zhiwei Zong , Bing Shen , Hanxi Luo , Chen Liu","doi":"10.1016/j.imlet.2025.107054","DOIUrl":"10.1016/j.imlet.2025.107054","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to analyse the expression of CD37 in different B cell subsets from human peripheral blood, exploring changes in CD37 expression in B cells of patients with primary Sjögren's syndrome (pSS) and assessing their clinical relevance.</div></div><div><h3>Methods</h3><div>A total of 32 pSS patients and age- and sex-matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated, and B cells were classified into five subsets using flow cytometry based on CD24 and CD38 expression. CD37 expression was evaluated, and functional differences between CD37+ and CD37- B cells were compared. Peripheral lymphocytes were stimulated with LPS to observe changes in CD37 expression. The expression of CD37 and related B cell subsets was also compared between pSS patients and healthy controls, followed by ROC curve analysis.</div></div><div><h3>Results</h3><div>CD37 was highly expressed in early-stage B cells, with a significant decrease in effector cells. CD37+ <em>B</em> cells exhibited higher proportions of CD40+, HLA-DR+, and IL-10+ cells, indicating enhanced antigen-presenting and regulatory capabilities. Post-LPS stimulation, CD37 expression significantly declined in pSS patients compared to healthy controls, suggesting increased sensitivity to differentiation into plasma cells. Additionally, CD37-related B cell subsets in pSS patients showed strong correlations with autoantibodies and immunological markers. ROC analysis revealed substantial areas under the curve, confirming the diagnostic potential of these subsets.</div></div><div><h3>Conclusion</h3><div>The expression of CD37 in B cell subsets is variable, indicating a potential regulatory role in B cell function and offering auxiliary diagnostic value in pSS.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107054"},"PeriodicalIF":3.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Maternal immune cell investigation from intervillous blood of placentas with chronic histiocytic intervillositis: Directions for future research 慢性组织细胞性绒毛间炎胎盘绒毛间血中母体免疫细胞的研究：未来的研究方向。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-10 DOI: 10.1016/j.imlet.2025.107053

Q. Lu , L.E. van der Meeren , M. Eikmans , M.L.P. van der Hoorn

引用次数: 0

Reactive oxygen species production by monocytes negatively correlates with disease activity in rheumatoid arthritis 类风湿关节炎中单核细胞活性氧的产生与疾病活动性呈负相关。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-08 DOI: 10.1016/j.imlet.2025.107052

Pablo Lores , Monique Costa , Anderson Saravia , Mercedes Landeira , Valeria da Costa , Santiago A. Rodríguez-Zraquia , M. Eugenia Cedrés , Juan Oliva , Guillermina Rado , Ignacio García , M. Florencia Festari , Sandra Consani , Carolina Díaz , Teresa Freire

{"title":"Reactive oxygen species production by monocytes negatively correlates with disease activity in rheumatoid arthritis","authors":"Pablo Lores , Monique Costa , Anderson Saravia , Mercedes Landeira , Valeria da Costa , Santiago A. Rodríguez-Zraquia , M. Eugenia Cedrés , Juan Oliva , Guillermina Rado , Ignacio García , M. Florencia Festari , Sandra Consani , Carolina Díaz , Teresa Freire","doi":"10.1016/j.imlet.2025.107052","DOIUrl":"10.1016/j.imlet.2025.107052","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint inflammation, synovial hyperplasia and degradation of the cartilage and bone in the joint. Patients with RA have an amplified T helper (Th) 1 and Th17 immune response and production of autoantibodies by autoreactive B cells. In the joint, macrophages mediate bone destruction and maintain the inflammatory process in RA. There is an increasing body of evidence indicating that NADPH oxidase (NOX2)-derived reactive oxygen species (ROS), mainly produced by macrophages and neutrophils, may have effector functions in RA.</div><div>In this work we characterized ROS production in both monocytes and macrophages in RA. Our results indicate that NOX2-dependent production of ROS attenuates inflammation and clinical signs by decreasing innate and adaptive immune responses in collagen-induced arthritis in mice. We also report that ROS production by circulating classical and non-classical monocytes from patients with RA negatively correlate with disease symptoms. Therefore, ROS produced by different monocyte subsets in peripheral blood might be considered as useful biomarkers or predictors of the immune response associated with RA disease activity.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107052"},"PeriodicalIF":3.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human keratinocytes exposed to a clinical strain of Leishmania tropica can result in parasite internalization 人类角化细胞暴露于热带利什曼原虫临床菌株可导致寄生虫内化。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-08 DOI: 10.1016/j.imlet.2025.107049

Imane El Idrissi Saik , Borja Prat-Luri , Yazmin Hauyon-La Torre , Meryem Lemrani , Myriam Riyad , Fabienne Tacchini-Cottier

{"title":"Human keratinocytes exposed to a clinical strain of Leishmania tropica can result in parasite internalization","authors":"Imane El Idrissi Saik , Borja Prat-Luri , Yazmin Hauyon-La Torre , Meryem Lemrani , Myriam Riyad , Fabienne Tacchini-Cottier","doi":"10.1016/j.imlet.2025.107049","DOIUrl":"10.1016/j.imlet.2025.107049","url":null,"abstract":"<div><div>Cutaneous Leishmaniasis (CL) due to <em>Leishmania tropica</em> is a public health burden in Morocco. The increasing clinical polymorphism challenges its proper diagnosis and treatment. Although the immunopathogenesis of CL due to L. <em>tropica</em> has been documented, the role of keratinocytes, a critical cell type in skin immunity, has never been investigated in this pathology. Overall, keratinocytes play a crucial role in the recognition and early immune response to <em>Leishmania</em> parasites upon skin inoculation, influencing the local immune response by producing early cytokines that shape anti-leishmanial immune responses. Moreover, they respond differently to each <em>Leishmania</em> species, influencing disease outcomes and helping create a unique microenvironment tailored to each species, thus affecting disease progression.</div><div>Herein, we have conducted <em>in vitro</em> infection of the human keratinocytes HaCaT cell line with Moroccan clinical strains of L. <em>tropica</em> and L. <em>major</em>. Through flow cytometry and imaging flow cytometry, we show that keratinocytes are infected with both <em>Leishmania</em> species and that they internalize L. <em>tropica</em> parasites. We also report that infection with L. <em>tropica</em> exhibits a higher infection frequency in keratinocytes compared to L. <em>major</em>. These findings support the potential involvement of keratinocytes in the early stages of cutaneous infection. However, further investigations are required to elucidate their role in modulating the local immune response. Our study is a first step in the investigation of keratinocytes involvement during CL due to L. <em>tropica</em> and opens new perspectives for research into CL-specific skin immune mechanisms.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107049"},"PeriodicalIF":3.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-125a-5p regulates Treg function by targeting Foxp3 in experimental autoimmune myasthenia gravis mice miR-125a-5p通过靶向Foxp3调控实验性自身免疫性重症肌无力小鼠Treg功能

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-07 DOI: 10.1016/j.imlet.2025.107050

Shuting Tan, Jingli Liu, Liuling Chen, Ruying Li, Jinpin Li

{"title":"miR-125a-5p regulates Treg function by targeting Foxp3 in experimental autoimmune myasthenia gravis mice","authors":"Shuting Tan, Jingli Liu, Liuling Chen, Ruying Li, Jinpin Li","doi":"10.1016/j.imlet.2025.107050","DOIUrl":"10.1016/j.imlet.2025.107050","url":null,"abstract":"<div><div>MicroRNAs are a class of endogenous noncoding small RNAs. miR-125a-5p is involved in immunoregulatory mechanisms in autoimmune diseases. Myasthenia gravis (MG) is an autoimmune disease in which regulatory T cells (Tregs) exhibit reduced numbers and functional defects, with decreased expression of the Treg cell-specific transcription factor Foxp3. Our previous study identified an abnormally high expression of miR-125a-5p in thymoma-associated myasthenia gravis, however, the involvement of miR-125a-5p in the pathogenesis of myasthenia gravis in vivo is unclear. In this study, we explored the role of thymic miR-125a-5p abnormalities in the pathogenesis of myasthenia gravis by establishing an experimental autoimmune myasthenia gravis model. Muscle strength score, low-frequency repetitive nerve stimulation, and serum acetylcholine receptor antibody were performed. The relative expression of miR-125a-5p and Foxp3 in the thymus and spleen was quantified, and the percentage of Treg cells, the levels of the inhibitory cytokines IL-10 and TGF-β1, and the proliferative capacity of splenic T lymphocytes were detected. Our findings revealed significant upregulation of miR-125a-5p expression in myasthenia gravis models. Reducing miR-125a-5p levels alleviated muscle weakness symptoms, elevated Foxp3 expression, enhanced the number of Treg cells, elevated the levels of the Treg-associated inhibitory cytokines IL-10 and TGF-β1, and inhibited the proliferative function of splenic T lymphocytes. The opposite result was obtained when miR-125a-5p was overexpressed. These results suggest that miR-125a-5p can inhibit Foxp3 expression, leading to a decrease in the number and abnormal function of Treg cells. Thus, our findings suggest that miR-125a-5p participates in the pathogenesis of myasthenia gravis by targeting Foxp3 to regulate the function of Treg cells, providing new insights to explore the immunoregulatory mechanisms of miR-125a-5p in myasthenia gravis.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107050"},"PeriodicalIF":3.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innate lymphoid cells: Dual roles and therapeutic opportunities in breast cancer 先天淋巴样细胞：乳腺癌的双重作用和治疗机会。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-06-07 DOI: 10.1016/j.imlet.2025.107051

Marija Mojić , Nataša Radulović , Simonida Bobić , Sandra Radenković , Aránzazu Cruz-Adalia , Ivana Stojanović

{"title":"Innate lymphoid cells: Dual roles and therapeutic opportunities in breast cancer","authors":"Marija Mojić , Nataša Radulović , Simonida Bobić , Sandra Radenković , Aránzazu Cruz-Adalia , Ivana Stojanović","doi":"10.1016/j.imlet.2025.107051","DOIUrl":"10.1016/j.imlet.2025.107051","url":null,"abstract":"<div><div>Innate lymphoid cells (ILC) play a crucial role in shaping immune responses and maintaining tissue homeostasis. Recent research has identified their involvement in breast cancer pathogenesis, mainly through shaping the tumor microenvironment, where they can exert dual roles, either promoting tumor eradication by enhancing anti-tumor immunity, or facilitating tumor progression through mechanisms of immune evasion. This functional plasticity makes ILC attractive targets for immunotherapy. Furthermore, their slow proliferation enables them to survive anti-proliferative radiation therapy and chemotherapy, which may support continuous immune surveillance of breast cancer tissue. However, this same resilience poses a significant challenge, as surviving ILC could contribute to tumor persistence or recurrence. Additionally, anti-estrogen therapy, chemotherapy and immune checkpoint inhibitors, commonly used in breast cancer treatment, may interfere with ILC function, either dampening their anti-tumor potential or enhancing their pro-tumor activities. Understanding the complex interactions between ILC and conventional therapies is critical for designing effective immunotherapeutic approaches that include ILC targeting, potentially overcoming resistance and improving patient outcomes in breast cancer therapy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107051"},"PeriodicalIF":3.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The emerging role of GlycoRNAs in immune regulation and recognition 糖rna在免疫调节和识别中的新作用。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-05-30 DOI: 10.1016/j.imlet.2025.107048

Nicole Montag , Pavlos Gousis , Jürgen Wittmann

{"title":"The emerging role of GlycoRNAs in immune regulation and recognition","authors":"Nicole Montag , Pavlos Gousis , Jürgen Wittmann","doi":"10.1016/j.imlet.2025.107048","DOIUrl":"10.1016/j.imlet.2025.107048","url":null,"abstract":"<div><div>Glycosylation, the enzymatic attachment of glycans to biomolecules, is a vital post-translational modification that impacts protein stability, immune recognition, and cellular communication. Traditionally associated with proteins and lipids, recent discoveries have revealed the existence of glycosylated RNAs (glycoRNAs), expanding our understanding of RNA modifications. GlycoRNAs challenge conventional paradigms by suggesting that glycosylation may regulate RNA stability, localization, and interactions with glycan-binding proteins, such as sialic acid-binding immunoglobulin-type lectins (Siglecs) and selectins. These interactions are particularly significant in the immune system, where glycosylation plays a key role in antigen recognition, immune cell trafficking, and pathogen detection.</div><div>The potential implications of glycoRNAs in immune regulation and disease are profound, with roles in autoimmune disorders, cancer, and infectious diseases. Advances in glycobiology, including mass spectrometry, RNA sequencing, glycan microarrays, and click chemistry technologies, are driving the growth of glycoRNA research and its translational applications. Understanding glycoRNAs could lead to new therapeutic opportunities, including glycoengineering, biomarker discovery, and targeted immune interventions. Despite challenges including low abundance and complex structure, research into glycoRNA is progressing rapidly, revealing their roles in immune responses and disease mechanisms. This review synthesizes the current knowledge on glycoRNAs, highlighting their emerging significance in immunology and outlining future research directions.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107048"},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DUSP14 attenuates airway inflammation and mucus hypersecretion in allergic asthma by regulating TAK1 activity DUSP14通过调节TAK1活性减轻变应性哮喘气道炎症和粘液高分泌。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-05-29 DOI: 10.1016/j.imlet.2025.107047

Rui Kong , Jun Bai , Qing Yao , Xiaoqing Xu

{"title":"DUSP14 attenuates airway inflammation and mucus hypersecretion in allergic asthma by regulating TAK1 activity","authors":"Rui Kong , Jun Bai , Qing Yao , Xiaoqing Xu","doi":"10.1016/j.imlet.2025.107047","DOIUrl":"10.1016/j.imlet.2025.107047","url":null,"abstract":"<div><div>Allergic asthma is characterized by persistent chronic airway inflammation, leading to mucus hypersecretion and airway hyperresponsiveness. Dual-specificity phosphatase 14 (DUSP14), a member of the DUSP family, is a key regulator in various biological processes. However, the function of DUSP14 in allergic asthma remains to be elucidated. In this study, we aim to explore the function and mechanism of DUSP14 in asthma-related airway inflammation. In an ovalbumin (OVA) asthma mouse model, DUSP14 was found to be significantly diminished. DUSP14 overexpression relieved airway inflammation and attenuated airway mucus production. <em>In vitro</em>, overexpression of DUSP14 attenuated IL-13-induced cellular inflammation and mucus hypersecretion in bronchial epithelial cells (BEAS-2B). Afterwards, we used the co-immunoprecipitation assay to confirm that DUSP14 interacted with TAK1. DUSP14 overexpression restrained the activation of TAK1 and NF-κB signaling pathway <em>in vitro</em> and <em>in vivo</em>. Taken together, our findings clearly showed that DUSP14 could alleviate airway inflammation by inhibiting TAK1 activity and NF-κB signaling pathway, positioning the DUSP14-TAK1-NF-κB regulatory axis as a potential therapeutic target for allergic asthma.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107047"},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electrostatic potential is the dominant force in antigenic selection of naïve T-cells and B-cells for activation and maturation 静电电位是naïve t细胞和b细胞在激活和成熟过程中抗原选择的主导力量。

IF 3.3 4区医学

Immunology letters Pub Date : 2025-05-23 DOI: 10.1016/j.imlet.2025.107037

Kripa N. Nand, Christopher Bystroff

{"title":"Electrostatic potential is the dominant force in antigenic selection of naïve T-cells and B-cells for activation and maturation","authors":"Kripa N. Nand, Christopher Bystroff","doi":"10.1016/j.imlet.2025.107037","DOIUrl":"10.1016/j.imlet.2025.107037","url":null,"abstract":"<div><div>Peptide antigenicity can be predicted from sequence using a simple method invented by Hopp and Woods in the early 1980′s. Since then, a much clearer understanding of T-cell/B-cell signaling and maturation calls for a new understanding of the amino acid determinants of antigenicity. We show that short peptides with more charged side chains generate significantly higher titers of peptide specific antibodies in co-immunized mice. Peptide docking simulations using linearized Poisson-Boltzmann calculations of electrostatic potential show that immunoglobulins distinguish the cognate peptide sequence from randomly selected sequences at \"arms length\" (10–20 Å) with >70 % of alternative sequences having higher energy at this distance, consistent with the weak specificity observed for naive T-cell and B-cell receptor interactions with MHC-bound antigen. Orders of magnitude lower complexity of the state space of charged surfaces as compared to the state space of surface shapes suggests a dominant role of electrostatics in selecting naive immune cells from the population of circulating cell lines. We propose a two-stage antigen recognition process, first electrostatic and then shape-based, that explains the dominant contribution of charged residues to peptide immunogenicity.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107037"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0