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Christopher P Nelson, Clett Erridge
Low-density lipoprotein cholesterol lowering, most notably via statin therapy, has successfully reduced the burden of coronary artery disease (CAD) in recent decades. However, the residual risk remaining even after aggressive lipid lowering has renewed interest in alternative targets. Anti-inflammatory drugs are thought to have much potential in this context, but side effects associated with long-term use of conventional anti-inflammatories, such as NSAIDs and glucocorticoids, preclude their use as preventive agents for CAD...
October 16, 2018: Immunogenetics
Yousuke Takahama, Izumi Ohigashi, Shigeo Murata, Keiji Tanaka
Positive selection of T cells in the thymus is induced by low-affinity TCR recognition of self-peptide-MHC complexes expressed by cortical thymic epithelial cells (cTECs). cTECs express a specialized type of proteasomes, the thymoproteasome, which generates a unique spectrum of MHC class I-associated peptides and plays a critical role in thymic positive selection of CD8+ T cells. However, it remains unclear how the thymoproteasome contributes to the thymic positive selection. More than 30 years ago, the "peptidic self" hypothesis proposed that TCRs recognize MHC-presented peptides only, without interacting with MHC molecules, which turned out to be incorrect...
October 15, 2018: Immunogenetics
Iris I de Winter, Tamar Qurkhuli, Nanine de Groot, Annemiek J M de Vos-Rouweler, Pim van Hooft, Ignas M A Heitkönig, Herbert H T Prins, Ronald E Bontrop, Gaby G M Doxiadis
The major histocompatibility complex (MHC) is a highly polymorphic and polygenic genomic region that plays a crucial role in immune-related diseases. Given the need for comparative studies on the variability of immunologically important genes among wild populations and species, we investigated the allelic variation of MHC class II DRB among three congeneric true lemur species: the red-fronted lemur (Eulemur rufifrons), red-bellied lemur (Eulemur rubriventer), and black lemur (Eulemur macaco). We noninvasively collected hair and faecal samples from these species across different regions in Madagascar...
October 15, 2018: Immunogenetics
Shukoofeh Torabi, Mona Tamaddon, Mojtaba Asadolahi, Gelareh Shokri, Rezvan Tavakoli, Nooshin Tasharrofi, Reza Rezaei, Vahid Tavakolpour, Hossein Sazegar, Fatemeh Kouhkan
MicroRNA-455-5p (miR-455-5p) seems to have an anti-inflammatory role in the immune system since its expression is induced by IL-10 cytokine. Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the central nervous system that is caused by an autoimmune inflammatory attack against the myelin insulation of neurons. The expression level of miR-455-5p and its role in MS pathogenesis has yet to be elucidated. We found that miR-455-5p expression was highly correlated with disease severity in MS patients...
October 11, 2018: Immunogenetics
Nel Otting, Natasja G de Groot, Ronald E Bontrop
The authors regret that an error was present in the Fig. 5 of the above article; some digits in the DRB allele-designations in Fig. 5 have been lost, and are incorrectly presented by only two digits. The correct allele-designations should have been four (or six) digits. The correct Figure is now presented correctly.
October 3, 2018: Immunogenetics
Weiping Zhou, Bin Gao, Shunyi Zhu
Defensins are small, cysteine-rich, cationic antimicrobial peptides, serving as effectors of the innate immune system and modulators of the adaptive immune system. They extensively exist in multicellular organisms and are divided into cis and trans according to their disulfide bridge connectivity patterns. It has been proposed that these two types of defensins convergently originated from different ancestors. Here, we report the discovery of a structural signature involved in the formation of the cysteine-stabilized α-helix/β-sheet (CSαβ) fold of the cis-defensins in some trans-β-defensins, with only one amino acid indel (CXC vs...
October 2, 2018: Immunogenetics
Jacqueline P Kurz, Zhou Yang, Robert B Weiss, David J Wilson, Kerry A Rood, George E Liu, Zhongde Wang
A decrease in the incidence of bovine mastitis, the costliest disease in the dairy industry, can be facilitated through genetic marker-assisted selective breeding programs. Identification of genomic variants associated with mastitis resistance is an ongoing endeavor for which genome-wide association studies (GWAS) using high-density arrays provide a valuable tool. We identified single nucleotide polymorphisms (SNPs) in Holstein dairy cattle associated with mastitis resistance in a GWAS by using a high-density SNP array...
September 30, 2018: Immunogenetics
Ianthe A E M van Belzen, Can Kesmir
Adoptive cell transfer (ACT) is a form of personalised immunotherapy which has shown promising results in metastasised cancer. For this treatment, autologous T lymphocytes are selected and stimulated in vitro before re-administration in large numbers. However, only a fraction of patients benefit from ACT, and it is not yet known what biomarkers can predict treatment outcome. In this review, we describe what tumour characteristics are associated with response to ACT. Based on the current knowledge, the best candidate biomarker for a good anti-tumour response seems to be a large number of neoantigens with a homogeneous distribution across the tumour in combination with sufficient MHC-I expression level...
September 20, 2018: Immunogenetics
Sylvie Guerder, Chervin Hassel, Alice Carrier
The lifespan of T cells is determined by continuous interactions of their T cell receptors (TCR) with self-peptide-MHC (self-pMHC) complexes presented by different subsets of antigen-presenting cells (APC). In the thymus, developing thymocytes are positively selected through recognition of self-pMHC presented by cortical thymic epithelial cells (cTEC). They are subsequently negatively selected by medullary thymic epithelial cells (mTEC) or thymic dendritic cells (DC) presenting self-pMHC complexes. In the periphery, the homeostasis of mature T cells is likewise controlled by the interaction of their TCR with self-pMHC complexes presented by lymph node stromal cells while they may be tolerized by DC presenting tissue-derived self-antigens...
September 17, 2018: Immunogenetics
Michael Basler, Jun Li, Marcus Groettrup
The immunoproteasome is expressed in cells of hematopoietic origin and is induced during inflammation by IFN-γ. Targeting the immunoproteasome with selective inhibitors has been shown to be therapeutically effective in pre-clinical models for autoimmune diseases, colitis-associated cancer formation, and transplantation. Immunoproteasome inhibition prevents activation and proliferation of lymphocytes, lowers MHC class I cell surface expression, reduces the expression of cytokines of activated immune cells, and curtails  T helper 1 and 17 cell differentiation...
September 15, 2018: Immunogenetics
Adrian Kelly, John Trowsdale
Immune response to disease requires coordinated expression of an army of molecules. The highly polymorphic MHC class I and class II molecules are key to control of specificity of antigen presentation. Processing of the antigen, to peptides or other moieties, requires other sets of molecules. For classical class I, this includes TAP peptide transporters, proteasome components and Tapasin, genes which are encoded within the MHC. Similarly, HLA-DO and -DM, which influence presentation by HLA class II molecules, are encoded in the MHC region...
September 13, 2018: Immunogenetics
Lin Zhang, Dongmei Lin, Sen Yu, Junping Bai, Wanchun Jiang, Wenzheng Su, Yanyan Huang, Shaohua Yang, Jiaqiang Wu
Major histocompatibility complex class I (MHC I) molecules are critically involved in defense against pathogens, and their high polymorphism is advantageous to a range of immune responses, especially in duck displaying biased expression of one MHC I gene. Here, we examined MHC I polymorphism in two duck (Anas platyrhynchos) breeds from China: Shaoxing (SX) and Jinding (JD). Twenty-seven unique UAA alleles identified from the MHC I genes of these breeds were analyzed concerning amino acid composition, homology, and phylogenetic relationships...
September 5, 2018: Immunogenetics
Ana Águeda-Pinto, Pedro José Esteves
The human S100A7 resides in the epidermal differentiation complex (EDC) and has been described as a key effector of innate immunity. In humans, there are five S100A7 genes located in tandem-S100A7A, S100A7P1, S100AL2, S100A7, and S100AP2. The presence of several retroelements in the S100A7A/S100A7P1 and S100A7/S100A7P2 clusters suggests that these genes were originated from a duplication around ~ 35 million years ago, during or after the divergence of Platyrrhini and Catarrhini primates. To test this hypothesis, and taking advantage of the high number of genomic sequences available in the public databases, we retrieved S100A7 gene sequences of 12 primates belonging to the Cercopithecoidea and Hominoidea (Catarrhini species)...
August 29, 2018: Immunogenetics
Nel Otting, Natasja G de Groot, Ronald E Bontrop
Chimpanzees have been used for some time as an animal model in research on immune-related diseases in humans. The major histocompatibility complex (MHC) region of the chimpanzee has also been the subject of studies in which the attention was mainly on the class I genes. Although full-length sequence information is available on the DRB region genes, such detailed information is lacking for the other class II genes and, if present, is based mainly on exon 2 sequences. In the present study, full-length sequencing was performed on DQ, DP, and DRA genes in a cohort of 67 pedigreed animals, thereby allowing a thorough analysis of the MHC class II repertoire...
August 29, 2018: Immunogenetics
Wiebke C Abels, Trishna Manandhar, Heike Kunze-Schumacher, Rainer Blasczyk, Christina Bade-Döding
Peptide selection in infected cells is not fully understood yet, but several indications point to the fact that there are differences to uninfected cells, especially in productive HCMV infection, since HCMV evolved various strategies to disable the hosts immune system, including presentation of peptide-HLA complexes to immune effector cells. Therefore, peptide predictions for specific HLA alleles are limited in these cases and the naturally presented peptide repertoire of HCMV-infected cells is of major interest to optimize adoptive T cell therapies...
August 21, 2018: Immunogenetics
María A Garrido, Teresa Rodriguez, Svitlana Zinchenko, Isabel Maleno, Francisco Ruiz-Cabello, Ángel Concha, Nicolás Olea, Federico Garrido, Natalia Aptsiauri
HLA class I (HLA-I) molecules play a crucial role in the presentation of tumor antigenic peptides to CD8+ T cells. Tumor HLA-I loss provides a route of immune escape from T cell-mediated killing. We analyzed HLA-I expression in 98 cryopreserved breast cancer tissues using a broad panel of anti-HLA-I antibodies. Genomic HLA-I typing was performed using DNA obtained from autologous normal breast tissue. Analysis of the loss of heterozygosity (LOH) in the HLA-I region of chromosome 6 (LOH-6) and in the β2-microglobulin (B2M) region of chromosome 15 (LOH-15) was done by microsatellite amplification of DNA isolated from microdissected tumor areas...
November 2018: Immunogenetics
N S Bardeskar, V Chavan, S Ahir-Bist, R Nanavati, P Samant-Mavani, P Mehta, Jayanti Mania-Pramanik
Human leukocyte antigen (HLA) molecules play a key role in regulating the immune response towards infectious agents like human immunodeficiency virus type-1 (HIV-1). They have been shown to influence transmission as well as the progression of HIV-1 towards acquired immune deficiency syndrome (AIDS). Roles of HLA-A and HLA-B have been documented extensively; however, HLA-C has been poorly studied. In the present study, we have evaluated the role of HLA-C in discordant couple and mother-to-child cohorts. HLA-C*07 was higher both in HIV-1-infected spouses and infants as compared to exposed uninfected spouses and infants...
November 2018: Immunogenetics
Keith T Ballingall, Ronald E Bontrop, Shirley A Ellis, Unni Grimholt, John A Hammond, Chak-Sum Ho, Jim Kaufman, Lorna J Kennedy, Giuseppe Maccari, Donald Miller, James Robinson, Steven G E Marsh
Significant progress has been made over the last decade in defining major histocompatibility complex (MHC) diversity at the nucleotide, allele, haplotype, diplotype, and population levels in many non-human species. Much of this progress has been driven by the increased availability and reduced costs associated with nucleotide sequencing technologies. This report provides an update on the activities of the comparative MHC nomenclature committee which is a standing committee of both the International Society for Animal Genetics (ISAG) and the International Union of Immunological Societies (IUIS) where it operates under the umbrella of the Veterinary Immunology Committee (VIC)...
November 2018: Immunogenetics
Taejoong Kim, Henry D Hunt, Mark S Parcells, Vicky van Santen, Sandra J Ewald
The function of the chicken's major histocompatibility complex (MHC or B complex) class I major (BF2) and minor (BF1) glycoproteins is compared for their expression, ability to present viral antigens to cytotoxic T lymphocytes (CTLs), and interaction with natural killer (NK) cells. MHC-restricted CTLs recognized virus antigen in the context of the BF2*21 major glycoprotein but not the BF1*21 minor glycoprotein. Marek's disease virus (MDV), a large DNA virus known to reduce the cell surface expression of class I glycoprotein, reduced the expression of BF2 glycoprotein while BF1glycoprotein expressions are remained as no change or slight increase...
September 2018: Immunogenetics
Jie Yang, Christina Vrettou, Tim Connelley, W Ivan Morrison
Granzymes are a family of serine proteases found in the lytic granules of cytotoxic T lymphocytes and natural killer (NK) cells, which are involved in killing of susceptible target cells. Most information on granzymes and their enzymatic specificities derive from studies in humans and mice. Although granzymes shared by both species show a high level of conservation, the complement of granzyme genes differs between the species. The aim of this study was to identify granzyme genes expressed in cattle, determine their genomic locations and analyse their sequences to predict likely functional specificities...
September 2018: Immunogenetics
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