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HIV HLA MHC

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https://www.readbyqxmd.com/read/29743316/hla-f-on-hla-null-721-221-cells-activates-primary-nk-cells-expressing-the-activating-killer-ig-like-receptor-kir3ds1
#1
Zahra Kiani, Franck P Dupuy, Julie Bruneau, Bertrand Lebouché, Cindy X Zhang, Elise Jackson, Irene Lisovsky, Sandrina da Fonseca, Daniel E Geraghty, Nicole F Bernard
NK cells elicit important responses against transformed and virally infected cells. Carriage of the gene encoding the activating killer Ig-like receptor KIR3DS1 is associated with slower time to AIDS and protection from HIV infection. Recently, open conformers of the nonclassical MHC class Ib Ag HLA-F were identified as KIR3DS1 ligands. In this study, we investigated whether the interaction of KIR3DS1 on primary NK cells with HLA-F on the HLA-null cell line 721.221 (221) stimulated KIR3DS1+ NK cells. We used a panel of Abs to detect KIR3DS1+ CD56dim NK cells that coexpressed the inhibitory NK cell receptors KIR2DL1/L2/L3, 3DL2, NKG2A, and ILT2; the activating NK cell receptors KIR2DS1/S2/S3/S5; and CCL4, IFN-γ, and CD107a functions...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29385169/fowlpoxvirus-recombinants-coding-for-the-ciita-gene-increase-the-expression-of-endogenous-mhc-ii-and-fowlpox-gag-pro-and-env-siv-transgenes
#2
Massimiliano Bissa, Greta Forlani, Carlo Zanotto, Giovanna Tosi, Carlo De Giuli Morghen, Roberto S Accolla, Antonia Radaelli
A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells...
2018: PloS One
https://www.readbyqxmd.com/read/29184023/effects-of-mutations-on-replicative-fitness-and-major-histocompatibility-complex-class-i-binding-affinity-are-among-the-determinants-underlying-cytotoxic-t-lymphocyte-escape-of-hiv-1-gag-epitopes
#3
Yushen Du, Tian-Hao Zhang, Lei Dai, Xiaojuan Zheng, Aleksandr M Gorin, John Oishi, Ting-Ting Wu, Janice M Yoshizawa, Xinmin Li, Otto O Yang, Otoniel Martinez-Maza, Roger Detels, Ren Sun
Certain "protective" major histocompatibility complex class I (MHC-I) alleles, such as B*57 and B*27, are associated with long-term control of HIV-1 in vivo mediated by the CD8+ cytotoxic-T-lymphocyte (CTL) response. However, the mechanism of such superior protection is not fully understood. Here we combined high-throughput fitness profiling of mutations in HIV-1 Gag, in silico prediction of MHC-peptide binding affinity, and analysis of intraperson virus evolution to systematically compare differences with respect to CTL escape mutations between epitopes targeted by protective MHC-I alleles and those targeted by nonprotective MHC-I alleles...
November 28, 2017: MBio
https://www.readbyqxmd.com/read/29046444/resistance-of-major-histocompatibility-complex-class-b-mhc-b-to-nef-mediated-downregulation-relative-to-that-of-mhc-a-is-conserved-among-primate-lentiviruses-and-influences-antiviral-t-cell-responses-in-hiv-1-infected-individuals
#4
Francis Mwimanzi, Mako Toyoda, Macdonald Mahiti, Jaclyn K Mann, Jeffrey N Martin, David Bangsberg, Mark A Brockman, Philip Goulder, Frank Kirchhoff, Zabrina L Brumme, Thumbi Ndung'u, Takamasa Ueno
Patient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate major histocompatibility complex class A (MHC-A) and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A, on average, 11 to 32% more efficiently than MHC-B...
January 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29023371/expression-profiles-of-ligands-for-activating-natural-killer-cell-receptors-on-hiv-infected-and-uninfected-cd4%C3%A2-%C2%BA-t-cells
#5
Alexandra Tremblay-McLean, Julie Bruneau, Bertrand Lebouché, Irene Lisovsky, Rujun Song, Nicole F Bernard
Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4- ) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV...
October 12, 2017: Viruses
https://www.readbyqxmd.com/read/29021373/a-specialist-macaque-mhc-class-i-molecule-with-hla-b-27-like-peptide-binding-characteristics
#6
Natasja G de Groot, Corrine M C Heijmans, Arnoud H de Ru, George M C Janssen, Jan W Drijfhout, Nel Otting, Christelle Vangenot, Gaby G M Doxiadis, Frits Koning, Peter A van Veelen, Ronald E Bontrop
In different macaque species, the MHC A2*05 gene is present in abundance, and its gene products are characterized by low cell-surface expression and a highly conserved peptide-binding cleft. We have characterized the peptide-binding motif of Mamu-A2*05:01, and elucidated the binding capacity for virus-derived peptides. The macaque A2*05 allotype prefers the basic amino acid arginine at the second position of the peptide, and hydrophobic and polar amino acids at the C-terminal end. These preferences are shared with HLA-B*27 and Mamu-B*008, molecules shown to be involved in elite control in human HIV type 1 and macaque SIV infections, respectively...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#7
Madhura Mukhopadhyay, Moran Galperin, Mandar Patgaonkar, Sandhya Vasan, David D Ho, Alexandre Nouël, Mathieu Claireaux, Daniela Benati, Olivier Lambotte, Yaoxing Huang, Lisa A Chakrabarti
Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4+ T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4+ T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28968755/evaluating-the-impact-of-functional-genetic-variation-on-hiv-1-control
#8
Paul J McLaren, Sara L Pulit, Deepti Gurdasani, Istvan Bartha, Patrick R Shea, Cristina Pomilla, Namrata Gupta, Effrossyni Gkrania-Klotsas, Elizabeth H Young, Norbert Bannert, Julia Del Amo, M John Gill, Jill Gilmour, Paul Kellam, Anthony D Kelleher, Anders Sönnerborg, Robert Zangerle, Frank A Post, Martin Fisher, David W Haas, Bruce D Walker, Kholoud Porter, David B Goldstein, Manjinder S Sandhu, Paul I W de Bakker, Jacques Fellay
Background: Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load...
November 27, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934310/sanger-and-next-generation-sequencing-data-for-characterization-of-ctl-epitopes-in-archived-hiv-1-proviral-dna
#9
Camille Tumiotto, Lionel Riviere, Pantxika Bellecave, Patricia Recordon-Pinson, Alice Vilain-Parce, Gwenda-Line Guidicelli, Hervé Fleury
One of the strategies for curing viral HIV-1 is a therapeutic vaccine involving the stimulation of cytotoxic CD8-positive T cells (CTL) that are Human Leucocyte Antigen (HLA)-restricted. The lack of efficiency of previous vaccination strategies may have been due to the immunogenic peptides used, which could be different from a patient's virus epitopes and lead to a poor CTL response. To counteract this lack of specificity, conserved epitopes must be targeted. One alternative is to gather as many data as possible from a large number of patients on their HIV-1 proviral archived epitope variants, taking into account their genetic background to select the best presented CTL epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28893287/natural-killer-nk-cell-receptor-hla-ligand-genotype-combinations-associated-with-protection-from-hiv-infection-investigation-of-how-protective-genotypes-influence-anti-hiv-nk-cell-functions
#10
REVIEW
Nicole F Bernard
The anti-HIV activity of natural killer (NK) cells could be induced fast enough to potentially prevent the establishment of HIV infection. Epidemiological studies identified two genotypes encoding NK receptors that contribute to NK cell function, that were more frequent in people who remained uninfected despite multiple HIV exposures than in HIV-susceptible subjects. NK cells from carriers of the *h/*y+B*57 genotype have higher NK cell functional potential and inhibit HIV replication in autologous HIV-infected CD4+ T cells (iCD4) more potently than those from carriers of non-protective genotypes...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28861087/alanine-mutagenesis-in-the-complementarity-determining-region-3-of-the-mtb-and-hiv-1-peptide-bispecific-t-cell-receptor-beta-chain-affects-ligand-recognition
#11
Chao-Ying Zhou, Rui-Ning Wang, Qian Wen, Wen-Ting He, Shi-Meng Zhang, Xia-Lin Du, Jia-Hui Yang, Li Ma
Mycobacterium tuberculosis/human immunodeficiency virus (MTB/HIV) coinfection presents a special challenge to the prevention and treatment of tuberculosis and HIV/AIDS. Adoptive transfer of high-affinity T cell receptor (TCR) gene-modified T cells against MTB and HIV antigens is a promising approach to treating MTB/HIV coinfected patients whose cellular immunity is obviously disordered. We have previously successfully identified that a bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using the complementarity determining region 3 (CDR3) spectratype analysis recognizes both MTB Ag85B199-207 and HIV-1 Env120-128 peptide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28772259/high-frequency-of-human-leukocyte-antigen-b-57-01-allele-carriers-among-hiv-infected-patients-in-serbia
#12
Marina Siljic, Dubravka Salemovic, Valentina Cirkovic, Ivana Pesic-Pavlovic, Marija Todorovic, Jovan Ranin, Gordana Dragovic, Djordje Jevtovic, Maja Stanojevic
Abacavir is an effective antiretroviral drug and one of the most commonly used nucleoside reverse transcriptase inhibitors in Serbia. А percentage of the treated patients experience a potentially life-threatening hypersensitivity reaction, which was shown to be associated with the presence of the class I MHC allele, HLA-B*57:01; hence genotyping for HLA-B*57:01 prior to starting abacavir is nowadays recommended in international HIV treatment guidelines. In Serbia, this testing became available in 2013. This study was designed to estimate the prevalence of the HLA-B*57:01 allele in Serbian HIV-1-infected patients...
2017: Intervirology
https://www.readbyqxmd.com/read/28649242/an-approach-for-a-synthetic-ctl-vaccine-design-against-zika-flavivirus-using-class-i-and-class-ii-epitopes-identified-by-computer-modeling
#13
Edecio Cunha-Neto, Daniela S Rosa, Paul E Harris, Tim Olson, Alex Morrow, Serban Ciotlos, Charles V Herst, Reid Martin Rubsamen
The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28615212/conserved-v%C3%AE-1-binding-geometry-in-a-setting-of-locus-disparate-phla-recognition-by-%C3%AE-%C3%AE-%C3%AE-tcrs-insight-into-recognition-of-hiv-peptides-by-tcr
#14
Yi Shi, Ai Kawana-Tachikawa, Feng Gao, Jianxun Qi, Chuansheng Liu, Jia Gao, Hao Cheng, Takamasa Ueno, Aikichi Iwamoto, George F Gao
Given a limited set of TCR V genes which are used to create TCRs that are reactive to different ligands, such as MHC class I, MHC class II and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vδ1 segment can be rearranged with Dδ-Jδ-Cδ or Jα-Cα segments, to form classical γδTCR or uncommon αβTCR using a Vδ1 segment (δ/αβTCR). Here we have determined two complex structures of the δ/αβTCRs (S19-2 and TU55) bound to different locus-disparate MHCIs with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28405623/bcg-vaccination-induces-hiv-target-cell-activation-in-hiv-exposed-infants-in-a-randomized-trial
#15
Melanie A Gasper, Anneke C Hesseling, Isaac Mohar, Landon Myer, Tali Azenkot, Jo-Ann S Passmore, Willem Hanekom, Mark F Cotton, I Nicholas Crispe, Donald L Sodora, Heather B Jaspan
BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4+ T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm)...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#16
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28110421/dendritic-cell-immune-responses-in-hiv-1-controllers
#17
REVIEW
Enrique Martin-Gayo, Xu G Yu
PURPOSE OF REVIEW: Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined...
February 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-major-histocompatibility-complex-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#18
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, the understanding of the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C-infected persons...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077649/t-cell-receptor-tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#19
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
Functional analysis of T-cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progressors. To define the role of individual T-cell receptor (TCR) clonotypes in differential antiviral CD8(+) T-cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T-cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28051183/hiv-1-env-associates-with-hla-c-free-chains-at-the-cell-membrane-modulating-viral-infectivity
#20
Michela Serena, Francesca Parolini, Priscilla Biswas, Francesca Sironi, Almudena Blanco Miranda, Elisa Zoratti, Maria Teresa Scupoli, Serena Ziglio, Agustin Valenzuela-Fernandez, Davide Gibellini, Maria Grazia Romanelli, Antonio Siccardi, Mauro Malnati, Alberto Beretta, Donato Zipeto
HLA-C has been demonstrated to associate with HIV-1 envelope glycoprotein (Env). Virions lacking HLA-C have reduced infectivity and increased susceptibility to neutralizing antibodies. Like all others MHC-I molecules, HLA-C requires β2-microglobulin (β2m) for appropriate folding and expression on the cell membrane but this association is weaker, thus generating HLA-C free-chains on the cell surface. In this study, we deepen the understanding of HLA-C and Env association by showing that HIV-1 specifically increases the amount of HLA-C free chains, not bound to β2m, on the membrane of infected cells...
January 4, 2017: Scientific Reports
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