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Journal of Virology, January 2003, p. 10-24, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.10-24.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Francois Villinger,1 Ann E. Mayne,1 Pavel Bostik,1 Kazuyasu Mori,2 Peter E. Jensen,1 Rafi Ahmed,3 and Aftab A. Ansari1*

Department of Pathology and Laboratory Medicine,1 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,3 AIDS Research Center, Tsukuba Primate Center for Medical Sciences, National Institute of Infectious Diseases, Tsukuba 305-0843, Japan2

Received 25 July 2002/ Accepted 30 September 2002

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.

* Corresponding author. Mailing address: Department of Pathology, Emory University School of Medicine, 2309 WMB, 1639 Pierce Dr., Atlanta, GA 30322. Phone: (404) 712-2834. Fax: (404) 712-1771. E-mail: pathaaa{at}emory.edu.

Journal of Virology, January 2003, p. 10-24, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.10-24.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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