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.
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.


CONCLUSIONS
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.
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia. martyn.french@uwa.edu.au
Martyn A
MA
French
Rob J
RJ
Center
Kim M
KM
Wilson
Ibrahim
I
Fleyfel
Sonia
S
Fernandez
Anna
A
Schorcht
Ivan
I
Stratov
Marit
M
Kramski
Stephen J
SJ
Kent
Anthony D
AD
Kelleher
D056704:Adaptive Immunity / Q000276:immunology*; D000483:Alleles; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology* / Q000503:physiopathology; D054884:Host-Pathogen Interactions; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D012367:RNA, Viral / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D012367:RNA, Viral; D017452:Receptors, IgG; D054301:gag Gene Products, Human Immunodeficiency Virus