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https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#1
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636593/t-cells-from-patients-with-parkinson-s-disease-recognize-%C3%AE-synuclein-peptides
#2
David Sulzer, Roy N Alcalay, Francesca Garretti, Lucien Cote, Ellen Kanter, Julian Agin-Liebes, Christopher Liong, Curtis McMurtrey, William H Hildebrand, Xiaobo Mao, Valina L Dawson, Ted M Dawson, Carla Oseroff, John Pham, John Sidney, Myles B Dillon, Chelsea Carpenter, Daniela Weiskopf, Elizabeth Phillips, Simon Mallal, Bjoern Peters, April Frazier, Cecilia S Lindestam Arlehamn, Alessandro Sette
Genetic studies have shown the association of Parkinson's disease with alleles of the major histocompatibility complex. Here we show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson's disease, act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson's disease. These responses may explain the association of Parkinson's disease with specific major histocompatibility complex alleles.
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636592/quantifiable-predictive-features-define-epitope-specific-t-cell-receptor-repertoires
#3
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi H O Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10(15) (ref. 1) to as high as 10(61) (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#4
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#5
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#6
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28632700/editorial-on-histocompatibility-section-2017
#7
Andrea A Zachary, Mary S Leffell
No abstract text is available yet for this article.
June 16, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28628857/identification-of-b-and-t-cell-epitope-based-peptide-vaccine-from-igf-1-receptor-in-breast-cancer
#8
Manijeh Mahdavi, Violaine Moreau, Majid Kheirollahi
The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28628037/alloimmune-t-cells-in-transplantation
#9
Susan DeWolf, Megan Sykes
Alloimmune T cells are central mediators of rejection and graft-versus-host disease in both solid organ and hematopoietic stem cell transplantation. Unique among immune responses in terms of its strength and diversity, the T cell alloresponse reflects extensive genetic polymorphisms between allogeneic donors and recipients, most prominently within the major histocompatibility complex (MHC), which encodes human leukocyte antigens (HLAs) in humans. The repertoire of alloreactive T cell clones is distinct for every donor-recipient pair and includes potentially thousands of unique HLA/peptide specificities...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28623392/mhc-class-i-diversity-in-chimpanzees-and-bonobos
#10
Vincent Maibach, Jörg B Hans, Christina Hvilsom, Tomas Marques-Bonet, Linda Vigilant
Major histocompatibility complex (MHC) class I genes are critically involved in the defense against intracellular pathogens. MHC diversity comparisons among samples of closely related taxa may reveal traces of past or ongoing selective processes. The bonobo and chimpanzee are the closest living evolutionary relatives of humans and last shared a common ancestor some 1 mya. However, little is known concerning MHC class I diversity in bonobos or in central chimpanzees, the most numerous and genetically diverse chimpanzee subspecies...
June 16, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28622932/an-evolutionary-medicine-perspective-on-neandertal-extinction
#11
Alexis P Sullivan, Marc de Manuel, Tomas Marques-Bonet, George H Perry
The Eurasian sympatry of Neandertals and anatomically modern humans - beginning at least 45,000 years ago and possibly lasting for more than 5000 years - has sparked immense anthropological interest into the factors that potentially contributed to Neandertal extinction. Among many different hypotheses, the "differential pathogen resistance" extinction model posits that Neandertals were disproportionately affected by exposure to novel infectious diseases that were transmitted during the period of spatiotemporal sympatry with modern humans...
July 2017: Journal of Human Evolution
https://www.readbyqxmd.com/read/28615693/the-ccr4-not-complex-contributes-to-repression-of-major-histocompatibility-complex-class-ii-transcription
#12
Alfonso Rodríguez-Gil, Olesja Ritter, Vera V Saul, Jochen Wilhelm, Chen-Yuan Yang, Rudolf Grosschedl, Yumiko Imai, Keiji Kuba, Michael Kracht, M Lienhard Schmitz
The multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) genes which are found in a gene cluster on chromosome 6...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615208/deficiency-of-the-nod-like-receptor-nlrc5-results-in-decreased-cd8-t-cell-function-and-impaired-viral-clearance
#13
Christopher R Lupfer, Kate L Stokes, Teneema Kuriakose, Thirumala-Devi Kanneganti
Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member, NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#14
Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
BACKGROUND: Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. METHODS: To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice...
June 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28611781/exploration-of-the-conformational-dynamics-of-major-histocompatibility-complex-molecules
#15
REVIEW
Saeko Yanaka, Kenji Sugase
Major histocompatibility complex (MHC) molecules are loaded with a wide variety of self- and non-self-peptides in their binding grooves and present these to T cell receptors (TCRs) in order to activate the adaptive immune system. A large number of crystal structures of different MHC alleles with different bound peptides have been determined, and they have been found to be quite similar to one another regardless of the bound peptide sequence. The structures do not change markedly even when forming complexes with TCRs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28610613/100-million-years-of-multigene-family-evolution-origin-and-evolution-of-the-avian-mhc-class-iib
#16
Julien Goebel, Marta Promerová, Francesco Bonadonna, Karen D McCoy, Céline Serbielle, Maria Strandh, Glenn Yannic, Reto Burri, Luca Fumagalli
BACKGROUND: Gene duplication has led to a most remarkable adaptation involved in vertebrates' host-pathogen arms-race, the major histocompatibility complex (MHC). However, MHC duplication history is as yet poorly understood in non-mammalian vertebrates, including birds. RESULTS: Here, we provide evidence for the evolution of two ancient avian MHC class IIB (MHCIIB) lineages by a duplication event prior to the radiation of all extant birds >100 million years ago, and document the role of concerted evolution in eroding the footprints of the avian MHCIIB duplication history...
June 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28608409/neoadjuvant-chemoradiotherapy-of-pancreatic-cancer-induces-a-favorable-immunogenic-tumor-microenvironment-associated-with-increased-major-histocompatibility-complex-class-i-related-chain-a-b-expression
#17
Takashi Murakami, Yuki Homma, Ryusei Matsuyama, Ryutaro Mori, Kentaro Miyake, Yusaku Tanaka, Kanechika Den, Yoji Nagashima, Masatoshi Nakazawa, Yukihiko Hiroshima, Michio Ueda, Kuniya Tanaka, Robert M Hoffman, Michael Bouvet, Itaru Endo
BACKGROUND: Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. METHODS: NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28608405/revisiting-the-specificity-of-the-mhc-class%C3%A2-ii-transactivator-ciita-in-classical-murine-dendritic-cells-in-vivo
#18
David A Anderson, Gary E Grajales-Reyes, Ansuman T Satpathy, Carlos E Vasquez Hueichucura, Theresa L Murphy, Kenneth M Murphy
Ciita was discovered for its role in regulating transcription of major histocompatibility complex class II (MHCII) genes. Subsequently, CIITA was predicted to control many other genes based on reporter and ChIP-seq analysis but few such predictions have been verified in vivo using Ciita(-/-) mice. Testing these predictions for classical dendritic cells (cDCs) has been particularly difficult, since Ciita(-/-) mice lack MHCII expression required to identify cDCs. However, recent identification of the cDC-specific transcription factor Zbtb46 allows identification of cDCs independently of MHCII expression...
June 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28603068/genetic-effects-on-hematopoietic-stem-cell-transplant-prognosis-and-outcomes-more-than-just-histocompatibility
#19
EDITORIAL
Jai N Patel, Lawrence J Druhan
No abstract text is available yet for this article.
June 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28602741/disease-resistance-and-response-against-vibrio-anguillarum-intestinal-infection-in-european-seabass-dicentrarchus-labrax-fed-low-fish-meal-and-fish-oil-diets
#20
S Torrecillas, M J Caballero, D Mompel, D Montero, M J Zamorano, L Robaina, F Rivero-Ramírez, V Karalazos, S Kaushik, M Izquierdo
The aim of this study was to assess the effects of low levels of dietary fish meal (FM) and fish oil (FO) on disease resistance and gut associated lymphoid tissue (GALT) response after an experimental intestinal infection with V. anguillarum in European sea bass (Dicentrarchus labrax) For that purpose, sea bass juveniles were fed one of four diets containing combined levels of FO and FM as follows: 20%FM/6%FO, 20%FM/3%FO, 5%FM/6%FO and 5%FM/3%FO during 153 days. At the end of the feeding trial, fish were subjected to either an in vivo exposure to a sub-lethal dose of V...
June 7, 2017: Fish & Shellfish Immunology
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