Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research

Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research

Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research

Leishmania surface molecule lipophosphoglycan-TLR2 interaction moderates TPL2-mediated TLR2 signalling for parasite survival
Immunology. 2023 Oct 17. doi: 10.1111/imm.13702. Online ahead of print.ABSTRACTLeishmania donovani, a protozoan parasite, resides and replicates in macrophages and inflicts the potentially fatal disease visceral leishmaniasis (VL). The parasite-expressed surface lipophosphoglycan (LPG) was implicated in binding TLR2 on NK cells, but the modus operandi of its disease-promoting influence remained unknown. As TPL2, a member of the MAPK module in mammalian macrophages, was implicated in the anti-inflammatory immune response and promoting pathogen survival, we investigated the possibility of TPL2-directed LPG-TLR2 signalling in...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Soumya Kanti Gosh Divanshu Shukla Hima Mahour Sunit Kumar Srivastava Neelam Bodhale Raja Banerjee Bhaskar Saha Source Type: research

The alterations of innate immunity and enhanced severity of infections in diabetes mellitus
Immunology. 2023 Oct 17. doi: 10.1111/imm.13706. Online ahead of print.ABSTRACTDiabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysi...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Zi Zhou Hao Wang Sipin Tan Huali Zhang Yaxi Zhu Source Type: research

Leishmania surface molecule lipophosphoglycan-TLR2 interaction moderates TPL2-mediated TLR2 signalling for parasite survival
Immunology. 2023 Oct 17. doi: 10.1111/imm.13702. Online ahead of print.ABSTRACTLeishmania donovani, a protozoan parasite, resides and replicates in macrophages and inflicts the potentially fatal disease visceral leishmaniasis (VL). The parasite-expressed surface lipophosphoglycan (LPG) was implicated in binding TLR2 on NK cells, but the modus operandi of its disease-promoting influence remained unknown. As TPL2, a member of the MAPK module in mammalian macrophages, was implicated in the anti-inflammatory immune response and promoting pathogen survival, we investigated the possibility of TPL2-directed LPG-TLR2 signalling in...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Soumya Kanti Gosh Divanshu Shukla Hima Mahour Sunit Kumar Srivastava Neelam Bodhale Raja Banerjee Bhaskar Saha Source Type: research

The alterations of innate immunity and enhanced severity of infections in diabetes mellitus
Immunology. 2023 Oct 17. doi: 10.1111/imm.13706. Online ahead of print.ABSTRACTDiabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysi...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Zi Zhou Hao Wang Sipin Tan Huali Zhang Yaxi Zhu Source Type: research

Leishmania surface molecule lipophosphoglycan-TLR2 interaction moderates TPL2-mediated TLR2 signalling for parasite survival
Immunology. 2023 Oct 17. doi: 10.1111/imm.13702. Online ahead of print.ABSTRACTLeishmania donovani, a protozoan parasite, resides and replicates in macrophages and inflicts the potentially fatal disease visceral leishmaniasis (VL). The parasite-expressed surface lipophosphoglycan (LPG) was implicated in binding TLR2 on NK cells, but the modus operandi of its disease-promoting influence remained unknown. As TPL2, a member of the MAPK module in mammalian macrophages, was implicated in the anti-inflammatory immune response and promoting pathogen survival, we investigated the possibility of TPL2-directed LPG-TLR2 signalling in...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Soumya Kanti Gosh Divanshu Shukla Hima Mahour Sunit Kumar Srivastava Neelam Bodhale Raja Banerjee Bhaskar Saha Source Type: research

The alterations of innate immunity and enhanced severity of infections in diabetes mellitus
Immunology. 2023 Oct 17. doi: 10.1111/imm.13706. Online ahead of print.ABSTRACTDiabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysi...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Zi Zhou Hao Wang Sipin Tan Huali Zhang Yaxi Zhu Source Type: research

Correction to "Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and na ïve primary health care workers upon COVID-19 vaccination"
Immunology. 2023 Oct 11. doi: 10.1111/imm.13689. Online ahead of print.NO ABSTRACTPMID:37821425 | DOI:10.1111/imm.13689 (Source: Immunology)
Source: Immunology - October 11, 2023 Category: Allergy & Immunology Source Type: research

Correction to "Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and na ïve primary health care workers upon COVID-19 vaccination"
Immunology. 2023 Oct 11. doi: 10.1111/imm.13689. Online ahead of print.NO ABSTRACTPMID:37821425 | DOI:10.1111/imm.13689 (Source: Immunology)
Source: Immunology - October 11, 2023 Category: Allergy & Immunology Source Type: research

Correction to "Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and na ïve primary health care workers upon COVID-19 vaccination"
Immunology. 2023 Oct 11. doi: 10.1111/imm.13689. Online ahead of print.NO ABSTRACTPMID:37821425 | DOI:10.1111/imm.13689 (Source: Immunology)
Source: Immunology - October 11, 2023 Category: Allergy & Immunology Source Type: research

Correction to "Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and na ïve primary health care workers upon COVID-19 vaccination"
Immunology. 2023 Oct 11. doi: 10.1111/imm.13689. Online ahead of print.NO ABSTRACTPMID:37821425 | DOI:10.1111/imm.13689 (Source: Immunology)
Source: Immunology - October 11, 2023 Category: Allergy & Immunology Source Type: research

Correction to "Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and na ïve primary health care workers upon COVID-19 vaccination"
Immunology. 2023 Oct 11. doi: 10.1111/imm.13689. Online ahead of print.NO ABSTRACTPMID:37821425 | DOI:10.1111/imm.13689 (Source: Immunology)
Source: Immunology - October 11, 2023 Category: Allergy & Immunology Source Type: research

Unlocking the role of the B7-H4 polymorphism in psoriasis: Insights into methotrexate treatment outcomes: A prospective cohort study
This study aims to investigate the effect of B7-H4 polymorphism on the efficacy of methotrexate (MTX) and its mechanism in psoriasis. Four single nucleotide polymorphisms of B7-H4 were genotyped in 310 psoriatic patients who received 12-week MTX. The protein expression of B7-H4 in platelets was characterized using immunofluorescence staining, confocal laser scanning microscopy, and flow cytometry techniques. We found that GG genotype carriers of B7-H4 rs1935780 had a lower Psoriasis Area and Severity Index (PASI) 75 response rate and higher weight (p = 0.0245) and body mass index (p = 0.0185) than AA and AG genotype carrie...
Source: Immunology - October 10, 2023 Category: Allergy & Immunology Authors: Bing Wang Zhicheng Wang Wenjing Yang Ling Han Qiong Huang Nikhil Yawalkar Zhenghua Zhang Yu Yao Kexiang Yan Source Type: research