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Mollie M Jurewicz, Lawrence J Stern
Presentation of peptide antigens by MHC-II proteins is prerequisite to effective CD4 T cell tolerance to self and to recognition of foreign antigens. Antigen uptake and processing pathways as well as expression of the peptide exchange factors HLA-DM and HLA-DO differ among the various professional and non-professional antigen-presenting cells and are modulated by cell developmental state and activation. Recent studies have highlighted the importance of these cell-specific factors in controlling the source and breadth of peptides presented by MHC-II under different conditions...
November 12, 2018: Immunogenetics
Keith T Ballingall, Kara Dicks, Panoraia Kyriazopoulou, Lynne Herrmann-Hoesing
The principal MHC class II molecules involved in the presentation of peptides to the antigen specific receptors on CD4+ T cells genes in sheep are derived from DR and DQ genes. Allelic nomenclature systems for the DRB1 and its partner DRA loci are available for Ovid's; however, no official nomenclature is available for the DQ genes which creates ambiguity within the research community. Ovine MHC haplotypes include at least two pairs of DQA and DQB genes, termed DQA1, DQB1 and DQA2, DQB2 and both sets are polymorphic and both seem to be functional...
November 10, 2018: Immunogenetics
Satoshi Ishido, Mizuho Kajikawa
Ubiquitination, a posttranscriptional modification, has been known to contribute to many aspects of cellular event (e.g., protein quality control, signal transduction). In 2007 and 2016, we reported physiological E3 ubiquitin ligases for MHC class II; these are membrane-associated ring-CH-type finger (MARCH)-1 and MARCH-8. Importantly, MARCH-1 and -8 are structurally close to each other, but have different expression profiles. MARCH-1 and -8 are expressed at secondary lymphoid organs and thymic epithelial cells, respectively...
October 31, 2018: Immunogenetics
Johannes M Dijkstra, Takuya Yamaguchi
Major histocompatibility complex (MHC) molecules are only found in jawed vertebrates and not in more primitive species. MHC class II type structures likely represent the ancestral structure of MHC molecules. Efficient MHC class II transport to endosomal compartments depends on association with a specialized chaperone, the MHC class II invariant chain (aliases Ii or CD74). The present study identifies conserved motifs in the CLIP region of CD74 molecules, used for binding in the MHC class II binding groove, throughout jawed vertebrates...
October 30, 2018: Immunogenetics
Amy L Ellis-Connell, Nadean M Kannal, Alexis J Balgeman, Shelby L O'Connor
The major histocompatibility complex (MHC) class I-related molecule, MR1, presents vitamin B metabolites from bacteria and yeast to mucosal-associated invariant T (MAIT) cells. Despite the evolutionary conservation of MR1, we do not know whether different allele variants of MR1 exist within the nonhuman primate (NHP) populations that are commonly used for biomedical research. In this study, we identified 21 distinct MR1 nucleotide sequences representing 32 different alleles across five different NHP populations...
October 23, 2018: Immunogenetics
Laura Santambrogio, Hans-Georg Rammensee
Every biological fluid, blood, interstitial fluid and lymph, urine, saliva, lacrimal fluid, nipple aspirate, and spinal fluid, contains a peptidome-degradome derived from the cellular secretome along with byproducts of the metabolic/catabolic activities of each parenchymal organ. Clement et al. (J Proteomics 78:172-187, 2013), Clement et al. (J Biol Chem 291:5576-5595, 2016), Clement et al. (PLoS One 5:e9863, 2010), Clement et al. (Trends Immunol 32:6-11, 2011), Clement et al. (Front Immunol 4:424, 2013), Geho et al...
October 20, 2018: Immunogenetics
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
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
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...
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
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