Antibody convergence along a common idiotypic axis in immunodeficiency virus and hepatitis C virus infections

The anti-idiotypic antibody 1F7 selectively binds antibodies against human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) gag, p ol, and env proteins. We tested antihepatitis C virus (HCV) antibodies to i nvestigate selection of the 1F7 idiotype on antibodies against other chroni c pathogens. Twelve of 15 HCV-seropositive individuals co-infected with HIV had detectable antibodies against recombinant HCV core, 4 against HCV NS4 protein, and 3 against HCV NS3 protein. All four HCV-sero positive, non-HIV -infected individuals had antibodies against HCV core and NS4, while 3 had antibodies against NS3. The 1F7 idiotype was frequently present on antibodi es against each of the HCV antigens in the HIV co-infected and non-HIV-infe cted groups. Antibodies against HCV, including antibodies recognizing the p utative principal neutralizing determinant of HCV E2 protein, displayed ske wed kappa/gimel light chain usage consistent with clonal dominance. These o bservations extend the association between expression of the 1F7 idiotype a nd abnormal B cell clonal dominance in HIV and SIV infection to HCV infecti on and suggest that early establishment of an oligoclonal antibody response against HCV may freeze the B cell repertoire, impair adaptation to emergen t HCV variants, and favor escape from neutralizing antibodies. We also demo nstrated that expression of the 1F7 idiotype extends beyond antibodies agai nst multiple antigens of AIDS-causing retroviruses to include antibodies ag ainst multiple antigens of an unrelated chronic hepatitis virus. Thus, dist inct pathogens establishing chronic infection in the face of strong humoral immune responses select antibodies along a common idiotypic axis of the im mune network. (C) 2002 Wiley-Liss, Inc.