IgG subclass responses to human immunodeficiency virus-1 antigens: lack of IgG2 response to gp41 correlates with clinical manifestation of disease.

To analyze differential antibody responsiveness of potential pathogenetic significance, sera from 66 patients with human immunodeficiency virus-1 (HIV-1) infections at various Walter Reed (WR) stages of the disease were analyzed to determine the subclass distribution of HIV antibodies. Although all IgG subclasses were involved in the HIV antibody response, the frequency was highest for IgG1 and the lowest for IgG4. When IgG subclass responses to different HIV antigens were compared qualitatively, IgG1 was the major subclass reactive with env, pol, and gag antigens; IgG2 and IgG3 were almost equally represented in response to gag gene products; and IgG4 showed minimal reactivity to p24 antigen in all HIV-infected patients regardless of their clinical presentation. In contrast, significantly lower levels of IgG2 anti-gp41 were observed in patients at WR 5 and 6 (5%) when compared to those at stage WR 1 and 2 (88%). The IgG2 response to a recombinant gp 120/41 antigen, however, remained unchanged, suggesting that the lack of IgG2 response may be associated with lack of responsiveness to the carbohydrate epitope on gp41. Indeed, parallel measurements of IgG antibody responses to group A carbohydrate were also lower in patients at WR 5 and 6 stages, without affecting antibody responses to polyribosyl ribitol phosphate and phosphocholine. As antibody responses to group A carbohydrate with its N-acetyl D-glucosamine (GlcNAc) determinant were lower at the WR 5 and 6 stage of HIV disease, GlcNAc may be one of the antigenic determinants on gp41 that plays a critical role in some of the pathologic events of HIV infection.