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 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 Neutralizing Antibodies in Sera from Macaques Immunized with Attenuated Simian Immunodeficiency Virus

1998 ◽  
Vol 72 (8) ◽  
pp. 6950-6955 ◽  
Author(s):  
Alphonse J. Langlois ◽  
Ronald C. Desrosiers ◽  
Mark G. Lewis ◽  
Vineet N. KewalRamani ◽  
Dan R. Littman ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Rhesus Macaques ◽  
Plasma Samples ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Virulent Virus ◽  
Established Cell ◽  
Resistance To Infection

ABSTRACT Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary SIVmac251 in CEMx174 cells that correlate with resistance to infection after experimental challenge with this virulent virus (M. S. Wyand, K. H. Manson, M. Garcia-Moll, D. C. Montefiori, and R. C. Desrosiers, J. Virol. 70:3724–3733, 1996). Here we show that these neutralizing antibodies are not detected in human and rhesus peripheral blood mononuclear cells (PBMC). In addition, neutralization of primary SIVmac251 in human and rhesus PBMC was rarely detected with plasma samples from a similar group of animals that had been infected either with SIVmac239Δnef for 1.5 years or with SIVmac239Δ3 for 3.2 years, although low-level neutralization was detected in CEMx174 cells. Potent neutralization was detected in CEMx174 cells when the latter plasma samples were assessed with laboratory-adapted SIVmac251. In contrast to primary SIVmac251, laboratory-adapted SIVmac251 did not replicate in human and rhesus PBMC despite its ability to utilize CCR5, Bonzo/STRL33, and BOB/gpr15 as coreceptors for virus entry. These results illustrate the importance of virus passage history and the choice of indicator cells for making assessments of neutralizing antibodies to lentiviruses such as SIV. They also demonstrate that primary SIVmac251 is less sensitive to neutralization in human and rhesus PBMC than it is in established cell lines. Results obtained in PBMC did not support a role for neutralizing antibodies as a mechanism of protection in animals immunized with attenuated SIV and challenged with primary SIVmac251.

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 The Simian Immunodeficiency Virus Envelope Glycoprotein Contains Two Epitopes Presented by the Mamu-A*01 Class I Molecule

1999 ◽  
Vol 73 (10) ◽  
pp. 8035-8039 ◽  
Author(s):  
Michelle Furchner ◽  
Ann L. Erickson ◽  
Todd Allen ◽  
David I. Watkins ◽  
Alessandro Sette ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Cytotoxic T Lymphocyte ◽  
Complex Molecule ◽  
Major Histocompatibility Complex Molecule ◽  
Class I ◽  
Coding Region ◽  
Virus Envelope ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus

ABSTRACT Cytotoxic T lymphocyte (CTL) responses against the simian immunodeficiency virus (SIV) envelope and Gag proteins were monitored in a Mamu-A*01-positive rhesus macaque infected with SIVsmE660. Peripheral blood mononuclear cells (PBMC) cultured with synthetic peptides spanning the entire gp160 and Gag coding region recognized a total of three epitopes. One located in Gag was identified as the previously described Mamu-A*01-restricted p11cC→M epitope (CTPYDINQM). The other two epitopes, designated p15m and p54m, were located in the gp160 envelope protein. Both were nine amino acids in length and were predicted to bind Mamu-A*01 because they contained proline and leucine residues at positions 3 and 9, respectively. Indeed, expression of this class I major histocompatibility complex molecule was required for target cell recognition by envelope-specific CD8+ T cells directed against both epitopes. These Mamu-A*01-restricted epitopes in the SIV envelope will be useful for monitoring immune responses in vaccinated or infected animals.

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