Quantitation of HLA Proteins Incorporated by Human Immunodeficiency Virus Type 1 and Assessment of Neutralizing Activity of Anti-HLA Antibodies

Abstract

Human anti-human leukocyte antigen (HLA) antibodies were assessed for neutralizing activity against human immunodeficiency virus type 1 (HIV-1) carrying HLA alleles with matching specificity. Multiparous women carrying anti-HLA antibodies were identified. Plasma samples from those women were confirmed as having antibodies that specifically bound to HLA proteins expressed on the peripheral blood mononuclear cells (PBMCs) of their husbands. A primary HIV-1 isolate was cultured in the husband's PBMCs so that the virus carried matching HLA alleles. To determine the HIV-1-neutralizing activity of anti-HLA antibodies, the infectivity of the virus for GHOST cells (which express green fluorescent protein after HIV infection) was investigated in the presence of a plasma sample positive for the respective anti-HLA antibody. A neutralization assay was also performed using purified immunoglobulin G (IgG) from two plasma samples, and two plasma samples were investigated in the presence of complement. The prerequisite for anti-HLA antibody-mediated neutralization is incorporation of HLA proteins by HIV-1. Therefore, the extent of incorporation of HLA proteins by the primary HIV-1 isolate was estimated. The ratios of HLA class I protein to HIV-1 capsid (p24) protein cultured in the PBMCs of two healthy individuals were 0.017 and 0.054. These ratios suggested that the HIV-1 strain used in the assay incorporated more HLA proteins than gp160 trimers. Anti-HLA antibodypositive plasma was found to contain antibodies that specifically reacted to HIV-1 carrying cognate HLA alleles. However, incubation of HIV-1 with anti-HLA antibody-positive plasma or purified IgG did not show a reduction in viral infectivity. HIV-1-neutralizing activity was also not detected in the presence of complement. This study shows that HIV-1 primary isolates cultured in PBMCs contain significant amounts of HLA proteins. However, the binding of antibodies to those HLA proteins does not mediate a reduction in viral infectivity.

Polyomavirus BK Neutralizing Activity in Human Immunoglobulin Preparations

“…Proof of principle that antibodies can be useful in targeting viral infection has been obtained for other viruses (15, 16). In addition to direct neutralization of virus, other potential mechanisms by which antibodies can exert a salutary effect include steric hindrance to receptor binding, conformational change in the bound protein, complement-dependent cytotoxicity, viral agglutination, and antibody facilitated phagocytosis (17–19). …”

HLA-C increases HIV-1 infectivity and is associated with gp120

“…Such an association may induce conformational changes of gp120 favouring the exposure of cryptic functional epitopes [ 12 ]. It has also been recently reported that viral particles carry more HLA molecules than gp120/gp41 trimers [ 21 ]. The association between a gp120/gp41 trimer and multiple HLA-C molecules might reduce gp120 shedding, thus keeping more functional the trimeric gp120/gp41 complexes on the viral envelope and resulting in increased fusion efficiency.…”

Induction of complement-mediated lysis of HIV-1 by a combination of HIV-specific and HLA allotype-specific antibodies

“…These results may partially explain previous data, which did not observe sufficient protection against SIV by immunizing macaques with transformed macaques B cells. Furthermore, a recent study demonstrated the absence of both complement-dependent and complement-independent neutralization of HLA-specific Abs against HIV carrying HLA alleles with matching specificity [30]. Therefore, our results may explain conflicting results from different studies indicating that the capacity of HLA allo-specific Abs generated by allo-immunization for the protection against HIV might depend on the feature of the generated Abs (e.g.…”