MHC-based vaccination approaches: progress and perspectives

2003 ◽  
Vol 5 (7) ◽  
pp. 1-17 ◽  
Author(s):  
Narinder K. Mehra ◽  
Gurvinder Kaur
Keyword(s):  
Geographical Location ◽  
Human Leukocyte ◽  
Vaccine Design ◽  
Hla Class I ◽  
Hiv Infections ◽  
Distribution Patterns ◽  
New Era ◽  
Geographical Population ◽  
Extended Haplotypes ◽  
Fast Progression

The major histocompatibility complex (MHC) harbours genes whose primary function in regulating immune responsiveness to infection is to present foreign antigens to cytotoxic T lymphocytes (CTLs) and T helper cells. In the case of infection by human immunodeficiency virus (HIV), defining the optimal HIV epitopes that are recognised by CTLs is important for vaccine design, and this in turn will depend on the characteristics of the predominant infecting virus. Moreover, the particular MHC human leukocyte antigens (HLAs) expressed by a geographical population is important since these are likely to determine which HIV epitopes are immunodominant in the anti-HIV immune response. Consideration of these aspects has lead to the dawn of a new era of MHC-based vaccine design, in which the CTL epitopes are selected on the basis of the frequency of restricting MHC alleles. This article reviews data on the distribution patterns of molecular subtypes of HLA class I and class II extended haplotypes, discussing distribution among Asian Indians but with reference to global distributions. These data provide a genetic basis for the possible predisposition and fast progression of HIV infections in the Indian population. Since there is selective predominance of different HLA alleles and haplotypes in different populations, a dedicated screening effort is required at the global level to develop MHC-based vaccines against infectious diseases. It is hoped that this might lead to the development of multivalent, poly-epitope, subtype-specific HIV vaccines that are specific for the target geographical location.

scholarly journals Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elham Ashouri ◽  
Karan Rajalingam ◽  
Shaghik Barani ◽  
Shirin Farjadian ◽  
Abbas Ghaderi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Cancer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Risk Scores ◽  
Hla Ligands ◽  
Nk Cytotoxicity

AbstractHuman leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.

scholarly journals Scyphomedusae and Ctenophora of the Eastern Adriatic: Historical Overview and New Data

Diversity ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 186
Author(s):  
Branka Pestorić ◽  
Davor Lučić ◽  
Natalia Bojanić ◽  
Martin Vodopivec ◽  
Tjaša Kogovšek ◽  
...  
Keyword(s):  
Adriatic Sea ◽  
Seasonal Pattern ◽  
Geographical Location ◽  
Distribution Patterns ◽  
Mnemiopsis Leidyi ◽  
Future Studies ◽  
Phenological Data ◽  
Pelagia Noctiluca ◽  
Regional Trends ◽  
Clear Seasonal Pattern

One of the obstacles to detecting regional trends in jellyfish populations is the lack of a defined baseline. In the Adriatic Sea, the jellyfish fauna (Scyphozoa and Ctenophora) is poorly studied compared to other taxa. Therefore, our goal was to collect and systematize all available data and provide a baseline for future studies. Here we present phenological data and relative abundances of jellyfish based on 2010–2019 scientific surveys and a “citizen science” sighting program along the eastern Adriatic. Inter-annual variability, seasonality and spatial distribution patterns of Scyphomedusae and Ctenophore species were described and compared with existing historical literature. Mass occurrences with a clear seasonal pattern and related to the geographical location were observed for meroplanktonic Scyphomedusae Aurelia solida, Rhizostoma pulmo, and to a lesser extent Chrysaora hysoscella, Cotylorhiza tuberculata and Discomedusa lobata. Holoplanktonic Pelagia noctiluca also formed large aggregations, which were seasonally less predictable and restricted to the central and southern Adriatic. Four species of Ctenophora produced blooms limited to a few areas: Bolinopsis vitrea, Leucothea multicornis, Cestum veneris and the non-native Mnemiopsis leidyi. However, differences between Adriatic subregions have become less pronounced since 2014. Our results suggest that gelatinous organisms are assuming an increasingly important role in the Adriatic ecosystem, which may alter the balance of the food web and lead to harmful and undesirable effects.

scholarly journals The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function

2020 ◽  
Vol 117 (21) ◽  
pp. 11636-11647 ◽  
Author(s):  
Philippa M. Saunders ◽  
Bruce J. MacLachlan ◽  
Phillip Pymm ◽  
Patricia T. Illing ◽  
Yuanchen Deng ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Peptide Binding ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Cell Recognition ◽  
Leukocyte Antigen ◽  
Binding Cleft

Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.

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.

scholarly journals Spondyloarthritis and the Human Leukocyte Antigen (HLA)-B*27 Connection

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengappa G. Kavadichanda ◽  
Jie Geng ◽  
Sree Nethra Bulusu ◽  
Vir Singh Negi ◽  
Malini Raghavan
Keyword(s):  
Endoplasmic Reticulum ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Clinical Aspects ◽  
Susceptibility Loci ◽  
New Bone Formation ◽  
High Association ◽  
Leukocyte Antigen ◽  
Heavy Chains

Heritability of Spondyloarthritis (SpA) is highlighted by several familial studies and a high association with the presence of human leukocyte antigen (HLA)-B*27. Though it has been over four decades since the association of HLA-B*27 with SpA was first determined, the pathophysiological roles played by specific HLA-B*27 allotypes are not fully understood. Popular hypotheses include the presentation of arthritogenic peptides, triggering of endoplasmic reticulum (ER) stress by misfolded HLA-B*27, and the interaction between free heavy chains or heavy chain homodimers of HLA-B*27 and immune receptors to drive IL-17 responses. Several non-HLA susceptibility loci have also been identified for SpA, including endoplasmic reticulum aminopeptidases (ERAP) and those related to the IL-23/IL-17 axes. In this review, we summarize clinical aspects of SpA including known characteristics of gut inflammation, enthesitis and new bone formation and the existing models for understanding the association of HLA-B*27 with disease pathogenesis. We also examine newer insights into the biology of HLA class I (HLA-I) proteins and their implications for expanding our understanding of HLA-B*27 contributions to SpA pathogenesis.

scholarly journals Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Yueran Li ◽  
Pooja Deshpande ◽  
Rebecca J. Hertzman ◽  
Amy M. Palubinsky ◽  
Andrew Gibson ◽  
...  
Keyword(s):  
T Cell ◽  
Predictive Value ◽  
Large Scale ◽  
Drug Hypersensitivity ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Therapeutic Interventions ◽  
Hypersensitivity Reactions ◽  
Prediction And Prevention

Adverse drug reactions (ADRs) remain associated with significant mortality. Delayed hypersensitivity reactions (DHRs) that occur greater than 6 h following drug administration are T-cell mediated with many severe DHRs now associated with human leukocyte antigen (HLA) risk alleles, opening pathways for clinical prediction and prevention. However, incomplete negative predictive value (NPV), low positive predictive value (PPV), and a large number needed to test (NNT) to prevent one case have practically prevented large-scale and cost-effective screening implementation. Additional factors outside of HLA contributing to risk of severe T-cell-mediated DHRs include variation in drug metabolism, T-cell receptor (TCR) specificity, and, most recently, HLA-presented immunopeptidome-processing efficiencies via endoplasmic reticulum aminopeptidase (ERAP). Active research continues toward identification of other highly polymorphic factors likely to impose risk. These include those previously associated with T-cell-mediated HLA-associated infectious or auto-immune disease such as Killer cell immunoglobulin-like receptors (KIR), epistatically linked with HLA class I to regulate NK- and T-cell-mediated cytotoxic degranulation, and co-inhibitory signaling pathways for which therapeutic blockade in cancer immunotherapy is now associated with an increased incidence of DHRs. As such, the field now recognizes that susceptibility is not simply a static product of genetics but that individuals may experience dynamic risk, skewed toward immune activation through therapeutic interventions and epigenetic modifications driven by ecological exposures. This review provides an updated overview of current and proposed genetic factors thought to predispose risk for severe T-cell-mediated DHRs.

scholarly journals High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

BMC Cancer ◽  
2009 ◽  
Vol 9 (1) ◽  
Author(s):  
David Cantú de León ◽  
Delia Pérez-Montiel ◽  
Verónica Villavicencio ◽  
Alejandro García Carranca ◽  
Alejandro Mohar Betancourt ◽  
...  
Keyword(s):  
Sporadic Breast Cancer ◽  
Case Control Study ◽  
Human Leukocyte ◽  
Breast Cancer Case ◽  
Hla Class I ◽  
Case Control ◽  
Cancer Case ◽  
Mexican Mestizo ◽  
Leukocyte Antigen ◽  
Control Study

Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, And Pathology

2018 ◽  
Author(s):  
Walter P Maksymowych
Keyword(s):  
Association Studies ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Population Based ◽  
Cell Phenotype ◽  
Imaging Data ◽  
Leukocyte Antigen ◽  
Seronegative Spondyloarthritis ◽  
Magnetic Resonance Imaging Mri

Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI. This review contains 8 figures, 5 tables and 33 references Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis

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.

Sign in / Sign up

Export Citation Format

Share Document