scholarly journals Single-cell derived tumor organoids display diversity in HLA class I peptide presentation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura C. Demmers ◽  
Kai Kretzschmar ◽  
Arne Van Hoeck ◽  
Yotam E. Bar-Epraïm ◽  
Henk W. P. van den Toorn ◽  
...  
Keyword(s):  
Damage Control ◽  
Colorectal Cancer Patient ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Peptide Ligands ◽  
Class I ◽  
Viable Option ◽  
Leukocyte Antigen ◽  
Peptide Presentation ◽  
Tumor Mutational Burden

Abstract Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system. While clone-specific differences in HLA peptide presentation were observed, broad inter-clone variability was even more prevalent (15–25%). By coupling organoid proteomics and HLA peptide ligandomics, we also found that tumor-specific ligands from DNA damage control and tumor suppressor source proteins were prominently presented by tumor cells, coinciding likely with the silencing of such cytoprotective functions. Collectively, these data illustrate the heterogeneous HLA peptide presentation landscape even within one individual, and hint that a multi-peptide vaccination approach against highly conserved tumor suppressors may be a viable option in patients with low tumor-mutational burden.

scholarly journals Multiple sclerosis: disease modifying therapy and the human leukocyte antigen

2018 ◽  
Vol 76 (10) ◽  
pp. 697-704 ◽  
Author(s):  
Lineu Cesar Werneck ◽  
Paulo José Lorenzoni ◽  
Cláudia Suemi Kamoi Kay ◽  
Rosana Herminia Scola
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Interferon Β ◽  
Leukocyte Antigen ◽  
Specific Subset ◽  
Hla Type ◽  
Disease Modifying

ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

Characteristics allelic of Human Leukocyte Antigen class I genotype and association with viral load and CD4 cell count in HIV-1 infected patients, Hanoi 2014 – 2016

2021 ◽  
Vol 31 (4) ◽  
pp. 43-50
Author(s):  
Tran Thi Minh Tam ◽  
Nguyen Thuy Linh ◽  
Phan Ha My ◽  
Nguyen Thi Lan Anh
Keyword(s):  
Viral Load ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cd4 Cell Count ◽  
Leukocyte Antigen ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Human Leukocyte Antigen (HLA) class I plays a regulatory role in cellular immune response to HIV-1 infection. The role of HLA alleles in HIV progression via viral load and CD4 cell count is well known. HLA class I is polymorphic and distributed differently by nation. This descriptive cross-sectional study was performed on 303 HIV-1 infected patients in 2014 - 2016, with aims to (i) characterize HLA class I genotype with 4-digit nomenclature and (ii) identify specifc alleles in correlate with CD4 cell counts and HIV viral load. 117 allele genotypes have been identifed, including 28 HLA-A alleles, 54 HLA-B alleles and 35 HLA-C alleles. The results showed that the most prevalent alleles in the population include A*11:01 (30.7%), B*15:02 (15.2%) and C*08:01 (17.1%). The frequency of haplotype created from these alleles is 8.4%. A*02:03, B*46:01 related to gender and ethnicity respectively. In conclusion, the study provided detailed pattern of HLA class I expression in a study population of HIV-1 infected patients and reported for the frst time the associated B*51:01, C*14:02 alleles associated to an increase in CD4 cell counts.

scholarly journals Human Leukocyte Antigen (HLA) class I and II datasets for sudanese

Data in Brief ◽  
2019 ◽  
Vol 24 ◽  
pp. 104027
Author(s):  
Ameer Mohamed Dafalla ◽  
Hisham Atan Edinur ◽  
Mohammed Abdelwahed ◽  
Almutaz Abbas Elemam ◽  
Amel Abdeen Ibrahim ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Leukocyte Antigen

Prognostic impact of PD-L1 expression in correlation with HLA class I expression status in stage I adenocarcinoma of the lung.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8548-8548
Author(s):  
Kazue Yoneda ◽  
Ayako Hirai ◽  
Shohei Shimajiri ◽  
Takeshi Hanagiri ◽  
Fumihiro Tanaka
Keyword(s):  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Stage I ◽  
Class I ◽  
Prognostic Impact ◽  
Leukocyte Antigen ◽  
Molecular Features ◽  
Poorly Differentiated

8548 Background: Programmed death-ligand 1 (PD-L1) and human leukocyte antigen (HLA) class-I, expressed on tumor cells (TCs), are important regulators in cancer immunity. The current study was conducted to assess prognostic impact of PD-L1 status in correlation with HLA class-I status in lung adenocarcinoma. Methods: A total of 94 patients with completely resected pathologic stage I lung adenocarcinoma were retrospectively reviewed. PD-L1 expression on TCs was evaluated with immunohistochemistry, in correlation with several clinicopathological and molecular features including HLA class-I expression on tumor TCs. Results: Seventeen patients (18.1%) had tumor with positive PD-L1 expression (percentage of TCs expressing PD-L1, ≥ 5%), and the incidence was higher in smokers with higher smoking index and in poorly differentiated tumor. There was no significant correlation between HLA class-I expression and PD-L1 expression. PD-L1-positivity was a significant factor to predict a poor survival (5-year survival rate, 66.7% versus 85.9%; P = 0.048), which was enhanced in tumor with normal HLA class-I expression (p = 0.029) but disappeared in tumor with reduced HLA class-I expression. Conclusions: The prognostic impact of PD-L1 expression on TCs in early-stage resectable lung adenocarcinoma was distinct according to HLA class-I expression on TCs.

scholarly journals A Viral, Transporter Associated with Antigen Processing (TAP)-independent, High Affinity Ligand with Alternative Interactions Endogenously Presented by the Nonclassical Human Leukocyte Antigen E Class I Molecule

2012 ◽  
Vol 287 (42) ◽  
pp. 34895-34903 ◽  
Author(s):  
Elena Lorente ◽  
Susana Infantes ◽  
David Abia ◽  
Eilon Barnea ◽  
Ilan Beer ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Antigen Processing ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Structural Motif ◽  
Leukocyte Antigen ◽  
High Affinity ◽  
Hla Class I Molecules ◽  
Infected Cells

The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8+ lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

scholarly journals Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans

PLoS Genetics ◽  
2013 ◽  
Vol 9 (10) ◽  
pp. e1003938 ◽  
Author(s):  
Paul J. Norman ◽  
Jill A. Hollenbach ◽  
Neda Nemat-Gorgani ◽  
Lisbeth A. Guethlein ◽  
Hugo G. Hilton ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Diverse Population ◽  
Leukocyte Antigen ◽  
Sub Saharan

scholarly journals In silico investigation of binding affinities between human leukocyte antigen class I molecules and SARS-CoV-2 virus spike and ORF1ab proteins

2021 ◽  
Author(s):  
Spyros A. Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
In Silico ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hla Class Ii ◽  
Class I ◽  
Binding Affinities ◽  
S Protein ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules

Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.

scholarly journals Immunogenetic Epidemiology of Dementia and Parkinson’s Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

2021 ◽  
Vol 5 (2) ◽  
pp. 16-26
Author(s):  
Lisa M. James ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
European Countries ◽  
Class I ◽  
Protective Mechanisms ◽  
Leukocyte Antigen ◽  
Epidemiology Of Dementia

Human leukocyte antigen (HLA), which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson’s disease. Here we report on the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of dementia and Parkinson’s disease in 14 Continental Western European countries, extending previous work1,2. We used these correlations to construct and compare HLA profiles for each disease3. We found that (a) the HLA profiles of the two diseases were significantly correlated across both HLA Class I and Class II alleles, (b) negative (“protective”) HLA-disease correlations did not differ significantly for either HLA class, but (c) positive (“susceptibility”) HLA-disease correlations were significantly higher in dementia than in Parkinson’s disease for both HLA classes of alleles. These findings indicate that (a) dementia and Parkinson’s disease share immunogenetic HLA-related mechanisms, (b) HLA-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c) HLA-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson’s disease.

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