Detection of anti-CD4 autoantibodies in the sera of HIV-infected patients using recombinant soluble CD4 molecules.

The use of purified recombinant soluble CD4 (sT4) allowed the detection of high titers of anti-CD4 immunoglobulins in the sera of three out of 33 HIV-infected patients. Binding of these antibodies to sT4 was first detected by enzyme-linked immunosorbent assay (ELISA), and their reactivity in the assay was blocked in a dose-dependent manner by preincubation with sT4. The antibodies could also immunoprecipitate iodinated sT4, but they failed to recognize CD4 expressed on the surface of CD4+ lymphocytes or cell lines. An ELISA which used as an antigen a truncated soluble CD4 molecule containing only the first two amino-terminal domains of the CD4 molecule did not react with these sera in ELISA, nor did it block antibody binding to sT4. Both these human sera and Leu3a, a mouse monoclonal antibody (mAb) which recognizes an epitope of CD4 close to the HIV binding site, failed to compete with one another for binding to sT4. Because these antibodies did not recognize epitope(s) of the CD4 molecule close to the HIV binding site, they are not likely to be anti-idiotypic antibodies directed against anti-HIV envelope antibodies. The exact location of the recognized epitope(s), as well as the role, if any, of these antibodies in the pathophysiology of HIV infection remains to be determined.