Isotype-switched immunoglobulin G antibodies to HIV Gag proteins may provide alternative or additional immune responses to protective human leukocyte antigen-B alleles in HIV controllers

French, Martyn A.; Center, Rob J.; Wilson, Kim M.; Fleyfel, Ibrahim; Fernandez, Sonia; Schorcht, Anna; Stratov, Ivan; Kramski, Marit; Kent, Stephen J.; Kelleher, Anthony D.

AIDS:
doi: 10.1097/QAD.0b013e32835cb720
Basic Science
Abstract

Background: Natural control of HIV infection is associated with CD8+ T-cell responses to Gag-encoded antigens of the HIV core and carriage of ‘protective’ human leukocyte antigen (HLA)-B alleles, but some HIV controllers do not possess these attributes. As slower HIV disease progression is associated with high levels of antibodies to HIV Gag proteins, we have examined antibodies to HIV proteins in controllers with and without ‘protective’ HLA-B alleles.

Methods: Plasma from 32 HIV controllers and 21 noncontrollers was examined for immunoglobulin G1 (IgG1) and IgG2 antibodies to HIV proteins in virus lysates by western blot assay and to recombinant (r) p55 and gp140 by ELISA. Natural killer (NK) cell-activating antibodies and FcγRIIa-binding immune complexes were also assessed.

Results: Plasma levels of IgG1 antibodies to HIV Gag (p18, p24, rp55) and Pol-encoded (p32, p51, p66) proteins were higher in HIV controllers. In contrast, IgG1 antibodies to Env proteins were less discriminatory, with only antigp120 levels being higher in controllers. High-level IgG2 antibodies to any Gag protein were most common in HIV controllers not carrying a ‘protective’ HLA-B allele, particularly HLA-B*57 (P = 0.016). HIV controllers without ‘protective’ HLA-B alleles also had higher plasma levels of IgG1 antip32 (P = 0.04). NK cell-activating antibodies to gp140 Env protein were higher in elite controllers but did not differentiate HIV controllers with or without ‘protective’ HLA-B alleles. IgG1 was increased in FcγRIIa-binding immune complexes from noncontrollers.

Conclusion: We hypothesize that isotype-switched (IgG2+) antibodies to HIV Gag proteins and possibly IgG1 antip32 may provide alternative or additional immune control mechanisms to HLA-restricted CD8+ T-cell responses in HIV controllers.

Author Information

aSchool of Pathology and Laboratory Medicine, University of Western Australia

bDepartment of Clinical Immunology, Royal Perth Hospital and PathWest, Laboratory Medicine, Perth, Western Australia

cDepartment of Microbiology and Immunology, University of Melbourne

dNRL, Melbourne, Victoria

eImmunovirology Laboratory, St. Vincent's Centre for Applied Medical Research, Sydney, New South Wales, Australia.

Correspondence to Martyn French, School of Pathology and Laboratory Medicine, Level 2, MRF Building, Rear, 50 Murray Street, Perth, 6000, Australia. Tel: +61 8 9224 0205; fax: +61 8 9224 0204; e-mail: martyn.french@uwa.edu.au

Received 27 June, 2012

Revised 26 October, 2012

Accepted 16 November, 2012

Copyright © 2013 Wolters Kluwer Health, Inc.