Novel simian immunodeficiency virus CTL epitopes restricted by MHC class I molecule Mamu-B*01 are highly conserved for long term in DNA/MVA-vaccinated, SHIV-challenged rhesus macaques

2005 ◽  
Vol 17 (5) ◽  
pp. 637-648 ◽  
Author(s):  
Jin Su ◽  
Mark A. Luscher ◽  
Yelin Xiong ◽  
Tarick Rustam ◽  
Rama Rao Amara ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Rhesus Macaques ◽  
Class I ◽  
Ctl Epitopes ◽  
Mhc Class I Molecule ◽  
Immunodeficiency Virus

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 CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing

2001 ◽  
Vol 75 (2) ◽  
pp. 738-749 ◽  
Author(s):  
Todd M. Allen ◽  
Bianca R. Mothé ◽  
John Sidney ◽  
Peicheng Jing ◽  
John L. Dzuris ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Mononuclear Cells ◽  
Class I ◽  
Binding Motif ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Immunodeficiency Virus

ABSTRACT It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8+ response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8+ epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*012, a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparentKd values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01+ macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.

scholarly journals Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

2007 ◽  
Vol 9 (1) ◽  
pp. 69-80 ◽  
Author(s):  
U Sauermann ◽  
R Siddiqui ◽  
Y-S Suh ◽  
M Platzer ◽  
N Leuchte ◽  
...  
Keyword(s):  
Survival Time ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Rhesus Macaques ◽  
Class I ◽  
Immunodeficiency Virus

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.

scholarly journals Evidence for Antibody-Mediated Enhancement of Simian Immunodeficiency Virus (SIV) Gag Antigen Processing and Cross Presentation in SIV-Infected Rhesus Macaques

2003 ◽  
Vol 77 (1) ◽  
pp. 10-24 ◽  
Author(s):  
Francois Villinger ◽  
Ann E. Mayne ◽  
Pavel Bostik ◽  
Kazuyasu Mori ◽  
Peter E. Jensen ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Immune Complexes ◽  
Antigen Processing ◽  
Mononuclear Cells ◽  
Rhesus Macaques ◽  
Class I ◽  
Peripheral Blood Mononuclear ◽  
Cross Presentation ◽  
Immunodeficiency Virus

ABSTRACT By using the dominant simian immunodeficiency virus (SIV) Gag Mamu-A01 restricted major histocompatibility complex (MHC) class I epitope p11CM, we demonstrate antibody-mediated enhanced MHC class I cross presentation of SIV Gag. In vitro restimulation of peripheral blood mononuclear cells from SIV-infected rhesus macaques with recombinant full-length SIV Gag p55 plus p55 affinity-purified immunoglobulin G (p55 Gag/p55-IgG) led to the generation of markedly higher frequencies of p11CM specific precursor cytotoxic T lymphocytes (p-CTLs) compared with restimulation with (i) SIV Gag p55 alone or (ii) optimal concentrations of the p11CM peptide alone. These results, along with the finding that CD4 depletion abrogated the enhancement, suggest a prominent role for CD4+ T cells. Testing for p-CTLs against other Mamu-A01-restricted SIV Gag epitopes suggested that this mechanism favored recognition of the dominant p11CM peptide, potentially further skewing of the CTL response. The p-CTL enhancing effect was also decreased or abrogated by pepsin digestion of the p55-specific IgG or by the addition of monoclonal antibodies to Fc receptor (FcR) II/III, suggesting that the effect was dependent on FcR-mediated uptake of the immune-complexed antigen. Finally, incubation of antigen-presenting cells with SIV Gag p55 immune complexes in the presence of lactacystin or of bafilomycin indicated that the mechanism of antibody-mediated enhancement of cross presentation required both the proteasomal and the endosomal pathways. These data demonstrate for the first time the cross presentation of antigens via immune complexes in lentiviral infection and indicate a heretofore-unrecognized role for antibodies in modulating the magnitude and potentially also the breadth of MHC class I-restricted antigen processing and presentation and CTL responses.

scholarly journals A Commonly Recognized Simian Immunodeficiency Virus Nef Epitope Presented to Cytotoxic T Lymphocytes of Indian-Origin Rhesus Monkeys by the Prevalent Major Histocompatibility Complex Class I Allele Mamu-A*02

2001 ◽  
Vol 75 (21) ◽  
pp. 10179-10186 ◽  
Author(s):  
Suzanne Robinson ◽  
William A. Charini ◽  
Michael H. Newberg ◽  
Marcelo J. Kuroda ◽  
Carol I. Lord ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Rhesus Monkey ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Rhesus Monkeys ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Mhc Class I Molecule ◽  
Immunodeficiency Virus

ABSTRACT The ability to monitor vaccine-elicited CD8+ cytotoxic T-lymphocyte (CTL) responses in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys has been limited by our knowledge of viral epitopes predictably presented to those lymphocytes by common rhesus monkey MHC class I alleles. We now define an SIV and SHIV Nef CTL epitope (YTSGPGIRY) that is presented to CD8+ T lymphocytes by the common rhesus monkey MHC class I molecule Mamu-A*02. All seven infectedMamu-A*02 + monkeys evaluated demonstrated this response, and peptide-stimulated interferon gamma Elispot assays indicated that the response represents a large proportion of the entire CD8+ T-lymphocyte SIV- or SHIV-specific immune response of these animals. Knowledge of this epitope and MHC class I allele substantially increases the number of available rhesus monkeys that can be used for testing prototype HIV vaccines in this important animal model.

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