IgG subclass profiles in infected HIV type 1 controllers and chronic progressors and in uninfected recipients of Env vaccines

Abstract

We have studied IgG subclass responses to the HIV-1 proteins gp120, gp41, p24, and Tat in individuals who control their infection without using antiretroviral drugs (HIV-1 controllers; HC) or who progress to disease (chronic progressors; CP). We also measured IgG subclass titers to gp120 in vaccinated individuals. In all cases, the IgG1 subclass dominated the overall response to each antigen. The only IgG titer that differed significantly between the HC and CP groups was to the p24 Gag protein, which was higher in the HC group. IgG1 titers to both p24 and gp120 were significantly higher in the HC group, and IgG3 anti-gp120 antibodies, although rare, were detected more frequently in that group than in CP. Overall, significantly more patients had IgG2 antibodies to gp120 than to gp41. Antibodies to other IgG subclasses were infrequent and their frequency or titers did not differ between the two patient groups. Anti-gp41 and anti-Tat responses also did not correlate with immune control, and anti-Tat antibodies were infrequently detected. Although we found isotypic differences in IgG responses to HIV-1 antigens among vaccinees and the HC and CP individuals, there were no indications of differential T(H)1:T(H)2 polarization between the different groups.

FIG. 1.

Specificity, cross-reactivity, and sensitivity tests for mouse antihuman IgG1, G2, G3, and G4 MAb conjugates. (A) gp120-binding MAbs of known IgG subclasses (IgG1-b12, IgG2-F425-B4e8, IgG3-447-52D) were used to compare the detection sensitivities of HRP-conjugated sheep antihuman IgG1 (1:1000), IgG2 (1:500), and IgG3 (1:1000) antibodies with that of an HRP-conjugated goat antihuman IgG polyclonal antibody (1:15,000) using a D7324-based gp120-capture ELISA. (B) HRP-conjugated sheep antihuman IgG1, IgG2, IgG3 [each at the same dilutions as in (A)], and IgG4 (1:500 dilution) antibodies were assessed for specificity and cross-reactivity using the same MAbs and ELISA format as in (A).

FIG. 2.

Anti-gp120 binding IgG subclass profiles in vaccinated individuals. (A) The D7324-based gp120-capture ELISA was used to assess anti-gp120 IgG endpoint titers in sera from 25 vaccinees or placebo recipients. The 20 samples in which anti-gp120 IgG could be detected and quantified were further assessed for IgG subclass titers. Each symbol represents the endpoint titer for one vaccinee; the horizontal bar is the median for the group. Nonresponders (titers <1.0 × 10²) are shown in the gray shaded area of the plot. (B–F) Correlations between IgG and IgG subclasses: r coefficients were calculated by Spearman's rank correlation.

FIG. 3.

Anti-gp120 IgG subclass profiles in the HC and CP groups. Endpoint titers of anti-gp120 IgG and IgG subclasses were assessed in plasma from 16 HC and 20 CP group members. Each symbol represents the titer for one individual; the horizontal bar is the median value for the group. Nonresponders (titers <1.0 × 10²) are shown in the gray shaded area of the plot.

FIG. 4.

Correlations between anti-gp120 IgG and IgG subclasses (A) and among individual subclasses (B) for the HC and CP groups. The r coefficients were calculated by Spearman's rank correlation.

FIG. 5.

Anti-gp41 IgG subclass profiles in the HC and CP groups. (A) The endpoint titers of IgG and IgG subclass antibodies to the gp41-N54 and gp41-SP400 peptides were assessed using plasma from 16 HC and 20 CP group members. Each symbol represents the titer for one individual; the horizontal bar is the median value for the group. Nonresponders (titers <1.0 × 10²) are shown in the gray shaded area of the plot. (B) Correlations between anti-gp41 IgG and IgG subclasses were investigated by Spearman's rank correlation.

FIG. 6.

Anti-p24 IgG subclass profiles in the HC and CP groups. (A) Endpoint titers of anti-p24 IgG and IgG subclasses were assessed in plasma from 16 HC and 20 CP group members. Each symbol represents the titer for one individual; the horizontal bar is the median value for the group. Nonresponders (titers <1.0 × 10²) are shown in the gray shaded area of the plot. (B) Correlations between anti-p24 IgG and IgG subclasses were investigated by Spearman's rank correlation.

FIG. 7.

Anti-Tat IgG subclass profiles in the HC and CP groups. Endpoint titers of anti-Tat IgG and IgG subclasses were assessed in plasma from 16 HC and 20 CP group members. Each symbol represents the titer for one individual; the horizontal bar is the median value for the group. Nonresponders (titers <1.0 × 10²) are shown in the gray shaded area of the plot.