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Human Immunology

Aimee L Hanson, Craig J Morton, Michael W Parker, Darrell Bessette, Tony J Kenna
The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their function, but how these variants contribute to disease remains largely unresolved...
November 9, 2018: Human Immunology
Mohamed Slimane, Christophe Picard, Jacques Chiaroni, Anderson Loundou, Julien Paganini, Pierre Tiberghien, Jean-Michel Rebibou, Julie Di Cristofaro
Factors determining anti-HLA immunization are poorly understood, although anti-HLA immunization following pregnancy is well described. The HLA-G molecule has been extensively described for its implication in immunological tolerance, especially during pregnancy. Transplant studies show an association between HLA-G haplotypes and alloimmunization. Our aim was to investigate the association of HLA-G haplotypes with anti-HLA class I and II immunization in a cohort of women having experienced one or more pregnancies and with no transfusion history...
November 7, 2018: Human Immunology
José A López de Castro, Efstratios Stratikos
Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) is an intracellular enzyme localized in the ER that has been shown to play roles in the generation of peptides that serve as ligands for MHC class I (MHC-1) molecules. Although ERAP2 has been primarily described as an accessory and complementary enzyme to the homologous ERAP1, several lines of evidence during the last few years suggest that it can play distinct and important roles in processing antigenic peptides and influencing cellular immune cytotoxic responses...
November 7, 2018: Human Immunology
Alicia Sanchez-Mazas, José Manuel Nunes
This paper discusses the advantages provided by next generation sequencing (NGS) compared to traditional typings or limited sequencing strategies for the characterization of HLA population diversity based on four documented examples. We also comment the limitations of this approach by highlighting pitfalls in interpreting NGS data.
November 2, 2018: Human Immunology
Yvonne Hagenlocher, Beatrix Willburger, Geoffrey A Behrens, Alexander H Schmidt, Yuri Ioffe, Jürgen Sauter
A total of 1075 Russians from the Russian part of Karelia were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next generation sequencing methods. The haplotypic and allelic profiles as well as Hardy-Weinberg proportions of this population sample were evaluated. As the most frequent 6-locus haplotype, A*03:01g∼B*07:02g∼C*07:02g∼DRB1*15:01g∼DQB1*06:02g∼DPB1* 04:01g was identified with an estimated frequency of 3.5 %. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied...
November 1, 2018: Human Immunology
B A González-Quezada, M G J Sánchez-Fernández, A J Munguía-Saldaña, M E Valencia-Macedo, H Flores-Aguilar, E Bonilla-Galán, A Rodríguez-Gómez, A Díaz-Rivera, C Gorodezky
Killer cell immunoglobulin-like receptors (KIRs), expressed on Natural Killer (NK) cells, activate/inhibit NK cell function through interactions with their HLA-A, B and C ligands. KIR3DL1 is one of the most polymorphic genes and its effect varies depending on the interaction of the specific allotype with its Bw4 ligand. We investigated the allelic diversity of KIR3DL1/S1 using sequence based typing and we typed as well, their Bw4 ligands in Mexican Mestizos of Mexico City. The results showed that this population has a great KIR3DL1 allelic diversity with ∗01502 (19...
October 23, 2018: Human Immunology
Tukisa Smith, Charlotte Cunningham-Rundles
Primary B-cell immunodeficiencies refer to diseases resulting from impaired antibody production due to either molecular defects intrinsic to B-cells or a failure of interaction between B-cells and T-cells. Patients typically have recurrent infections and can vary with presentation and complications depending upon where the defect has occurred in B-cell development or the degree of functional impairment. In this review, we describe B-cell specific immune defects categorized by presence or absence of peripheral B-cells, immunoglobulins isotypes and evidence of antibody impairment...
October 22, 2018: Human Immunology
Hyoeun Shim, Boram Park, Hye-Jin Shin, Jungnam Joo, Kyong-Ah Yoon, Young Min Kim, Tomonori Hayashi, Katsushi Tokunaga, Sun-Young Kong, Joo-Young Kim
Human leukocyte antigen (HLA) class II alleles have been previously associated with cervical cancer. However, these associations vary widely across racial and ethnic groups. Therefore, we evaluated the effect of HLA class II alleles on cervical cancer in a Korean population. HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles were analyzed in 457 cervical cancer patients and compared to those of 926 control subjects. The odds ratio (OR) of each allele between the patients and controls was calculated using the logistic regression model...
October 20, 2018: Human Immunology
Xiaofei Lv, Xialian Tang, Jinbin Lai, Wenhui Ye, Guang Shao, Changqing Lin, Xicai Wu, Xili Yang
In this work, we carried out a case-control study to examine the role of CTLA4 49 A→G (rs231775), IL1B -511 C→T (rs16944), IL10 -1082 A→G (rs1800896), IL10 -592 A→C (rs1800872), IL12B 3'UTR 1188 A→C (rs 3212227) and IL18 105 A→C (rs549908) polymorphisms on the risk of Hashimoto's thyroiditis among Han Chinese. The six polymorphisms were genotyped on 1,114 patients with Hashimoto's thyroiditis and 1,308 age- and sex-matched controls. Odds ratios (ORs) were then calculated via logistic regression model to determine the association present...
October 13, 2018: Human Immunology
Effie W Petersdorf, Colm O'hUigin
The MHC continues to have the most disease-associations compared to other regions of the human genome, even in the genome-wide association study (GWAS) and single nucleotide polymorphism (SNP) era. Analysis of non-coding variation and their impact on the level of expression of HLA allotypes has shed new light on the potential mechanisms underlying HLA disease associations and alloreactivity in transplantation. Next-generation sequencing (NGS) technology has the capability of delineating the phase of variants in the HLA antigen-recognition site (ARS) with non-coding regulatory polymorphisms...
October 12, 2018: Human Immunology
Jacques Thibodeau, Mohamed Abdelwafi Moulefera, Renaud Balthazard
Classical HLA class II molecules are highly polymorphic heterodimeric transmembrane proteins encoded by a polygenic cluster on chromosome 6. Polymorphic residues in the membrane-distal domains ensure that a large collection of microbial peptides can be bound in the human population. Still, the HLA-DR, -DP and -DQ isotypes show a high degree of conservation in their overall tertiary and quaternary structures, in line with their common function in T cell receptor activation. Interestingly, the primary structure of the intracellular domains are highly divergent between isotypes and they also show allotypic variations...
October 12, 2018: Human Immunology
Maneesh K Misra, Danillo G Augusto, Gonzalo Montero Martin, Neda Nemat-Gorgani, Jürgen Sauter, Jan A Hofmann, James A Traherne, Betsy González-Quezada, Clara Gorodezky, Will P Bultitude, Wesley Marin, Cynthia Vierra-Green, Kirsten M Anderson, Antonio Balas, Jose L Caro-Oleas, Elisa Cisneros, Francesco Colucci, Ravi Dandekar, Sally M Elfishawi, Marcelo A Fernández-Viña, Merhan Fouda, Rafael González-Fernández, Arend Große, Maria J Herrero-Mata, Sam Q Hollenbach, Steven G E Marsh, Alex Mentzer, Derek Middleton, Ashley Moffett, Miguel A Moreno-Hidalgo, Ghada I Mossallam, Annettee Nakimuli, Jorge R Oksenberg, Stephen J Oppenheimer, Peter Parham, Maria-Luiza Petzl-Erler, Dolores Planelles, Florentino Sánchez-García, Francisco Sánchez-Gordo, Alexander H Schmidt, John Trowsdale, Luciana B Vargas, Jose L Vicario, Carlos Vilches, Paul J Norman, Jill A Hollenbach
The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3...
October 12, 2018: Human Immunology
Elizabeth S Allen, Bing Yang, Jodi Garrett, Edward D Ball, Martin Maiers, Gerald P Morris
Matching of human leukocyte antigen (HLA) genes is critically important in hematopoietic stem cell transplantation (HSCT). HLA genes are highly polymorphic and HLA matching has historically been limited by technologies that are unable to unambiguously determine HLA genotypes. Next generation DNA sequencing (NGS) overcomes these limitations by enabling near full-gene sequences with phase determination for heterozygous alleles. Here we examine the efficacy and utility of HLA-NGS in the clinical setting. In a 54-sample validation study and 955 patient samples subsequently tested using HLA-NGS, we observed significant improvement in the ability to unambiguously identify HLA genotypes in both the validation (97...
October 11, 2018: Human Immunology
Zhendong Zhu, Yunmei Zhang, Jiyun Ye, Xuechang Wang, Xuemei Fu, Yan Yin, Jin Wen, Xinran Wu, Zhonghua Xia
Interleukin (IL)-35 is a heterodimeric cytokine composed of the IL-12A subunit and the Epstein-Barr virus induced gene 3 (EBI3) subunit. Binding of IL-35 with IL-12 receptor subunit beta 2 (IL-12RB2) and IL-6 signal transducer (IL-6ST) occupies the binding sites of IL-6, IL-12, and IL-27 and prevents their signal transduction. IL-35 is also shown to promote the development of regulatory T cells (Tregs) and regulatory B cells (Bregs). In this study, we investigated B cell-mediated IL-35 production in patients with coronary artery disease (CAD)...
October 11, 2018: Human Immunology
Steven G E Marsh
No abstract text is available yet for this article.
October 11, 2018: Human Immunology
Steven G E Marsh
No abstract text is available yet for this article.
October 11, 2018: Human Immunology
Steven G E Marsh
No abstract text is available yet for this article.
October 11, 2018: Human Immunology
Eugene Moore, Alba Grifoni, Daniela Weiskopf, Veronique Schulten, Cecilia S Lindestam Arlehamn, Michael Angelo, John Pham, Shay Leary, John Sidney, David Broide, April Frazier, Elizabeth Phillips, Simon Mallal, Steven J Mack, Alessandro Sette
DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1 loci was performed on 496 healthy adult donors from San Diego, California, to characterize allele frequencies in support of studies of T cell responses to common allergens. Deviations from Hardy Weinberg proportions were detected at each locus except A and C. Several alleles were found in more than 15% of individuals, including the class II alleles DPB1∗02:01, DPB1∗04:01, DQA1∗01:02, DQA1∗05:01, DQB1∗03:01, and the class I allele A∗02:01...
September 29, 2018: Human Immunology
Hasan Mollanoori, Hojat Shahraki, Yazdan Rahmati, Shahram Teimourian
Clustered regularly interspaced short palindromic repeats/CRISPR associated nuclease9 (CRISPR/Cas9) technology, an acquired immune system in bacteria and archaea, has provided a new tool for accurately genome editing. Using only a single nuclease protein in complex with 2 short RNA as a site-specific endonuclease made it a simple and flexible genome editing tool to target nearly any genomic locus. Due to recent developments in therapeutic engineered T cell and effective responses of CD19-directed chimeric antigen receptor T cells (CART19) in patients with B-cell leukemia and lymphoma, adoptive T cell immunotherapy, particularly CAR-T cell therapy became a rapidly growing field in cancer therapy and recently Kymriah and Yescarta (CD19-directed CAR-T cells) were approved by FDA...
September 24, 2018: Human Immunology
Hellen Caroline Issler, Leonardo Maldaner Amorim, Maria Luiza Petzl-Erler, Luciana Debortoli de Carvalho, Hadany Dorea Bezerra, Jomar Fagundes Júnior, Sandra Rocha Gadelha, Danillo G Augusto
We here describe the KIR gene-content genotypes in the highly admixed population from Ilhéus, a city located in Bahia State, Northeast Brazil. Bahia is the State with the largest contribution of African ethnicity in comparison to other Brazilian areas and this is the first report of a population from this region. A total of 32 KIR gene-content genotypes have been found, from which 18 were observed in single individuals. The distinct KIR gene-content distribution observed in Ilhéus, along with the elevated diversity of genotypes point to importance of describing KIR polymorphism in unique populations from Brazil...
September 22, 2018: Human Immunology
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