Molecular specificities of CD4+ T cell-reactive IgM in human immunodeficiency virus (HIV-1) infection.
The molecular targets and biological properties of lymphocytotoxic sera in 11 human immunodeficiency virus (HIV)+ subjects in CDC stages II to IVC were investigated. A purified soluble CEM membrane used as the CD4+ T cell clonotypic model in immunoblotting techniques revealed a homogeneous pattern of IgM-mediated reactivity to a 43.5-kDa membrane component in 10 sera. Conversely, CEM membrane-reactive IgG from these sera were weakly reactive to various antigens with no prevalent specificity. ELISA assay against purified 25.5-, 43.5-, and 60.8-kDa CEM membrane antigens revealed a significant affinity of IgM from sera 3, 8, 9, and 10 for the 43.5-kDa receptor, thus confirming the high specificity of these cytotoxic antibodies for their substrate. Additional experiments included the idiotypic saturation of purified IgM molecules with increasing amounts of the 43.5-kDa antigen. Functional inhibition of CEM-reactive IgM by their antigen was dose-dependent. The maximum inhibition of the ELISA reactivity was detected at 1/7 antigen/antibody concentration. By contrast, a significant decline of cytotoxic properties of sera 8, 9, and 10 to CEM lymphoblasts was noted only when equivalent concentrations of the 43.5-kDa receptor and purified IgM were incubated. In addition, the 43.5-kDa antigen appeared to be the preferential target of cytotoxic IgM in HIV-1 infection, since purified cytotoxic IgM from two SLE patients were not inhibited by this molecule. Our data provide specific molecular support for earlier evidence of exacerbation by T cell-reactive antibodies of the lymphopenia associated with HIV-1 infection.
Silvestris
F
F
Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Italy.
Cafforio
P
P
Romito
A
A
Dammacco
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015497:HIV-1; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D015728:Receptors, HIV / Q000502:physiology; D012680:Sensitivity and Specificity
D007075:Immunoglobulin M; D015728:Receptors, HIV