scholarly journals MHC genotyping from rhesus macaque exome sequences

2019 ◽  
Author(s):  
John R. Caskey ◽  
Roger W. Wiseman ◽  
Julie A. Karl ◽  
David A. Baker ◽  
Taylor Lee ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Mhc Class I ◽  
Rhesus Macaques ◽  
Class Ii ◽  
Class I ◽  
Target Enrichment ◽  
High Confidence ◽  
Protein Coding ◽  
Histocompatibility Complex ◽  
Mhc Genotyping

AbstractIndian rhesus macaque major histocompatibility complex (MHC) variation can influence the outcomes of transplantation and infectious disease studies. Frequently, rhesus macaques are MHC genotyped to identify variants that could account for unexpected results. Since the MHC is only one region in the genome where variation could impact experimental outcomes, strategies for simultaneously profiling variation in the macaque MHC and the remainder of the protein coding genome would be useful. Here we introduce macaque exome sequence (MES) genotyping, in which MHC class I and class II genotypes are determined with high confidence using target-enrichment probes that are enriched for MHC sequences. For a cohort of 27 Indian rhesus macaques, we describe two methods for obtaining MHC genotypes from MES data and demonstrate that the MHC class I and class II genotyping results obtained with these methods are 98.1% and 98.7% concordant, respectively, with expected MHC genotypes. In contrast, conventional MHC genotyping results obtained by deep sequencing of short multiplex PCR amplicons were only 92.6% concordant with expectations for this cohort.

scholarly journals The Major Histocompatibility Complex of Old World Camels—A Synopsis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1200 ◽  
Author(s):  
Plasil ◽  
Wijkmark ◽  
Elbers ◽  
Oppelt ◽  
Burger ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Old World ◽  
Histocompatibility Complex ◽  
Mhc Class Iii ◽  
Antigen Presenting

This study brings new information on major histocompatibility complex (MHC) class III sub-region genes in Old World camels and integrates current knowledge of the MHC region into a comprehensive overview for Old World camels. Out of the MHC class III genes characterized, TNFA and the LY6 gene family showed high levels of conservation, characteristic for MHC class III loci in general. For comparison, an MHC class II gene TAP1, not coding for antigen presenting molecules but functionally related to MHC antigen presenting functions was studied. TAP1 had many SNPs, even higher than the MHC class I and II genes encoding antigen presenting molecules. Based on this knowledge and using new camel genomic resources, we constructed an improved genomic map of the entire MHC region of Old World camels. The MHC class III sub-region shows a standard organization similar to that of pig or cattle. The overall genomic structure of the camel MHC is more similar to pig MHC than to cattle MHC. This conclusion is supported by differences in the organization of the MHC class II sub-region, absence of functional DY genes, different organization of MIC genes in the MHC class I sub-region, and generally closer evolutionary relationships of camel and porcine MHC gene sequences analyzed so far.

scholarly journals Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma

2018 ◽  
Vol 36 (10) ◽  
pp. 942-950 ◽  
Author(s):  
Margaretha G.M. Roemer ◽  
Robert A. Redd ◽  
Fathima Zumla Cader ◽  
Christine J. Pak ◽  
Sara Abdelrahman ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Histocompatibility Complex ◽  
Classic Hodgkin Lymphoma ◽  
Programmed Death ◽  
Clinical Responses ◽  
Programmed Death 1 ◽  
Cell Expression

Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti–PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components—β2-microglobulin, MHC class I, and MHC class II—by immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. Results Patients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a > 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.

Peripheral Nerve Myelin Modulates the Effect of Antidepressants on Major Histocompatibility Complex Expression on Macrophages in Experimental Allergic Neuritis

1995 ◽  
Vol 8 (3) ◽  
pp. 185-198 ◽  
Author(s):  
J. Zhu ◽  
B.-O. Bengtsson ◽  
E. Mix ◽  
L.-H. Thorell ◽  
T. Olsson ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Peripheral Nerve ◽  
Mhc Class I ◽  
Class Ii ◽  
Class I ◽  
Experimental Allergic Neuritis ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Experimental Allergic ◽  
Allergic Neuritis

The effect of bovine peripheral nerve myelin (BPM) used for induction of experimental allergic neuritis (EAN) in Lewis rats, on antidepressants' modulation of interferon-gamma (IFN-γ)-induced major histocompatibility complex (MHC) class I and II antigen expression on peritoneal macrophages in EAN rats was studied. Antidepressants with different profiles concerning inhibition of the neuronal reuptake of the monoamines serotonin (5-HT) and noradrenalin (NA), respectively, in concentrations of 10−4 to 10−8 M were used. At the concentration of 1.0 U/ml IFN-γ, most antidepressants significantly enhanced both MHC class I and class II expression, except maprotiline, a selective NA reuptake inhibiting antidepressant that suppressed MHC class I expression. Zimeldine, a selective 5-HT reuptake inhibitor did not affect MHC class II expression. BPM in general had an enhancing effect on modulation of both MHC class I and class II expression by antidepressants. By itself BPM enhanced MHC class I expression, but did not affect class II expression at IFN-γ 1.0 U/ml. The modulating effect of BPM on regulation of MHC expression by antidepressants could be the result of contaminating T cells and release of IFN-γ into cultures. The modulatory effect of antidepressants on MHC expression may to some extent be exerted by the action on 5-HT and/or NA regulation, but also by direct effects of antidepressants on macrophages. They probably play a role in zimeldine-induced Guillain-Barré syndrome in some patients and in the suppression of clinical signs of EAN in Lewis rats reported for some antidepressants.

scholarly journals Mamu-B*08-Positive Macaques Control Simian Immunodeficiency Virus Replication

2007 ◽  
Vol 81 (16) ◽  
pp. 8827-8832 ◽  
Author(s):  
John T. Loffredo ◽  
Jess Maxwell ◽  
Ying Qi ◽  
Chrystal E. Glidden ◽  
Gretta J. Borchardt ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Rhesus Macaques ◽  
Chronic Phase ◽  
Class I ◽  
Immune Protection ◽  
Elite Controllers ◽  
Specific Primers ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT Certain major histocompatibility complex (MHC) class I alleles are associated with the control of human immunodeficiency virus and simian immunodeficiency virus (SIV) replication. We have designed sequence-specific primers for detection of the rhesus macaque MHC class I allele Mamu-B*08 by PCR and screened a cohort of SIV-infected macaques for this allele. Analysis of 196 SIVmac239-infected Indian rhesus macaques revealed that Mamu-B*08 was significantly overrepresented in elite controllers; 38% of elite controllers were Mamu-B*08 positive compared to 3% of progressors (P = 0.00001). Mamu-B*08 was also associated with a 7.34-fold decrease in chronic phase viremia (P = 0.002). Mamu-B*08-positive macaques may, therefore, provide a good model to understand the correlates of MHC class I allele-associated immune protection and viral containment in human elite controllers.

scholarly journals Major histocompatibility complex (MHC) fragment numbers alone – in Atlantic cod and in general - do not represent functional variability

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 963 ◽  
Author(s):  
Johannes M. Dijkstra ◽  
Unni Grimholt
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Fish Species ◽  
Teleost Fish ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Speciation Rates

This correspondence concerns a publication by Malmstrøm et al. in Nature Genetics in October 2016. Malmstrøm et al. made an important contribution to fish phylogeny research by using low-coverage genome sequencing for comparison of 66 teleost (modern bony) fish species, with 64 of those 66 belonging to the species-rich clade Neoteleostei, and with 27 of those 64 belonging to the order Gadiformes. For these 66 species, Malmstrøm et al. estimated numbers of genes belonging to the major histocompatibility complex (MHC) class I lineages U and Z and concluded that in teleost fish these combined numbers are positively associated with, and a driving factor of, the rates of establishment of new fish species (speciation rates). They also claimed that functional genes for the MHC class II system molecules MHC IIA, MHC IIB, CD4 and CD74 were lost in early Gadiformes. Our main criticisms are (1) that the authors did not provide sufficient evidence for presence or absence of intact functional MHC class I or MHC class II system genes, (2) that they did not discuss that an MHC subpopulation gene number alone is a very incomplete measure of MHC variance, and (3) that the MHC system is more likely to reduce speciation rates than to enhance them. We conclude that their new model of MHC class I evolution, reflected in their title “Evolution of the immune system influences speciation rates in teleost fish”, is unsubstantiated. In addition, we explain that their “pinpointing” of the functional loss of the MHC class II system and all the important MHC class II system genes to the onset of Gadiformes is preliminary, because they did not sufficiently investigate the species at the clade border.

Invasive equine trophoblast expresses conventional class I major histocompatibility complex antigens

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 63-71
Author(s):  
W.L. Donaldson ◽  
C.H. Zhang ◽  
J.G. Oriol ◽  
D.F. Antczak
Keyword(s):  
Monoclonal Antibodies ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Antigen Expression ◽  
Class Ii ◽  
Class I ◽  
Trophoblast Cells ◽  
Histocompatibility Complex ◽  
Mhc Class I Antigens ◽  
Mhc Class I Antigen

Monoclonal antibodies and alloantisera were used in an indirect immunohistochemical assay to determine the expression of class I and class II Major Histocompatibility Complex (MHC) antigens by equine placental cells and the endometrial tissues at the fetal-maternal interface. MHC class I antigens were expressed at high density on the surface of the trophoblast cells of the chorionic girdle at days 32–36, just prior to their invasion of the endometrium. The mature gonadotrophin-secreting cells of the endometrial cups, which are derived from the chorionic girdle cells, had greatly reduced levels of MHC class I antigen expression while no MHC class I antigens were detectable on the non-invasive trophoblast cells of the allantochorion, except in small isolated patches. MHC class I antigens immunoprecipitated from chorionic girdle cells with either monoclonal antibodies or alloantisera had a relative molecular mass of 44,000, which was identical to that of MHC class I antigens precipitated from lymphocytes with the same reagents. MHC class II antigens were not detected on any trophoblast cells, although they were expressed at high levels by the endometrial glandular and lumenal epithelium immediately bordering the endometrial cups. MHC class I antigens were also expressed at high levels by endometrial tissues in the area of the cups. The high level of MHC class I antigen expression by endometrial glands within and bordering the cups was in sharp contrast to the greatly reduced class I antigen expression by the mature endometrial cup cells themselves.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression

2000 ◽  
Vol 74 (16) ◽  
pp. 7400-7410 ◽  
Author(s):  
David T. Evans ◽  
Peicheng Jing ◽  
Todd M. Allen ◽  
David H. O'Connor ◽  
Helen Horton ◽  
...  
Keyword(s):  
Disease Progression ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Rhesus Macaques ◽  
Class I ◽  
Ctl Epitopes ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Mhc Class I Molecules

ABSTRACT Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently the best animal model for AIDS vaccine development. One limitation of this model, however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and restricting major histocompatibility complex (MHC) class I molecules available for investigating virus-specific CTL responses. To identify new MHC class I-restricted CTL epitopes, we infected five members of a family of MHC-defined rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four different MHC class I molecules were defined. These included two Env epitopes bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04, and -B*17. All four restricting MHC class I molecules were encoded on only two haplotypes (b or c). Interestingly, resistance to disease progression within this family appeared to be associated with the inheritance of one or both of these MHC class I haplotypes. Two individuals that inherited haplotypes b and cseparately survived for 299 and 511 days, respectively, while another individual that inherited both haplotypes survived for 889 days. In contrast, two MHC class I-identical individuals that did not inherit either haplotype rapidly progressed to disease (survived <80 days). Since all five offspring were identical at their Mamu-DRBloci, MHC class II differences are unlikely to account for their patterns of disease progression. These results double the number of SIV CTL epitopes defined in rhesus macaques and provide evidence that allelic differences at the MHC class I loci may influence rates of disease progression among AIDS virus-infected individuals.

scholarly journals Efficient Class I Major Histocompatibility Complex Down-Regulation by Simian Immunodeficiency Virus Nef Is Associated with a Strong Selective Advantage in Infected Rhesus Macaques

2001 ◽  
Vol 75 (21) ◽  
pp. 10532-10536 ◽  
Author(s):  
Jan Münch ◽  
Nicole Stolte ◽  
Dietmar Fuchs ◽  
Christiane Stahl-Hennig ◽  
Frank Kirchhoff
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Rhesus Macaques ◽  
Selective Advantage ◽  
Class I ◽  
Down Regulation ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV) Nef to down-modulate major histocompatibility complex (MHC) class I from the cell surface but has no effect on other Nef functions, such as down-regulation of CD4, CD28, and CD3 cell surface expression or stimulation of viral replication and enhancement of virion infectivity. Inoculation of three rhesus macaques with the SIVmac239 Y223F-Nef variant revealed that this point mutation consistently reverts and that Nef activity in MHC class I down-modulation is fully restored within 4 weeks after infection. Our results demonstrate a strong selective pressure for a tyrosine at amino acid position 223 in SIV Nef, and they constitute evidence that Nef-mediated MHC class I down-regulation provides a selective advantage for viral replication in vivo.

Synergistic induction of HLA class I expression by RelA and CIITA

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3804-3808 ◽  
Author(s):  
John Girdlestone
Keyword(s):  
Transcription Factors ◽  
Mhc Class I ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Promoter Elements ◽  
Cooperative Action ◽  
Histocompatibility Complex ◽  
Synergistic Induction ◽  
Necrosis Factor

The major histocompatibility complex (MHC) class I genes are induced synergistically by interferons (IFN) and tumor necrosis factor (TNF) , a response thought to involve the cooperative action of Rel/NF-kB and interferon regulatory factor (IRF) transcription factors. The IFN-γ–inducible class II transcriptional activator (CIITA) has recently been shown to transactivate MHC class I as well as class II genes, and this investigation shows that CIITA synergizes strongly with RelA to stimulate HLA class I expression. The functional interaction of CIITA and RelA requires both promoter elements and the upstream Rel binding site and is not seen with a class II reporter. The promoter elements necessary for CIITA action are also required for induction by IFN-. HLA-A and HLA-B loci respond differentially to IFNs, and we identify locus-specific differences in critical promoter elements in addition to known polymorphisms in the Rel and IRF binding sites. The HLA-A promoter is transactivated relatively poorly by CIITA and does not interact detectably with CREB proteins implicated in CIITA recruitment, but the synergism with RelA can compensate for this weakness. The present findings illustrate that multiple transcription factors cooperate to regulate class I expression and that their relative importance differs according to the locus and cell type examined.

Sign in / Sign up

Export Citation Format

Share Document