Human antibodies to major histocompatibility complex alloantigens mediate lysis and neutralization of HIV-1 primary isolate virions in the presence of complement.
Cellular proteins, including major histocompatibility complex (MHC) class I and class II antigens, are incorporated into the membrane of HIV-1 when virions bud from infected cells. Experiments were performed to determine whether human sera that contained MHC class I and/or class II antibodies would lyse or neutralize a primary isolate of HIV. These results demonstrate that in the presence of complement, sera from some alloimmunized persons mediated significant anti-viral activity against an HIV primary isolate. Both lysis and neutralization of virus were observed. The antiviral effects were complement dependent because heat inactivation eliminated most anti-viral effects. Antiviral activity mediated by sera containing MHC alloantibodies in the presence of complement was > or = activity due to sera from HIV-infected persons as reported in this and a previous study. High levels of antibodies to both MHC class I and class II were present in sera that mediated the highest levels of anti-viral activity. Absorption of serum with platelets (which express class I but not class II antigens) substantially reduced their lytic activity. These studies suggest that MHC antibodies mediate potent anti-viral effects on primary isolates of HIV and support the possibility that deliberately alloimmunizing humans might protect against HIV infection.
Rush-Presbyterian-St. Luke's Medical Center, Department of Immunology/Microbiology, 1653 West Congress Parkway, Chicago, Illinois 60612, USA. gspear@rush.edu
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Spear
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Olinger
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Saifuddin
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Gebel
D000906:Antibodies / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000494:pharmacology; D000937:Antigen-Antibody Reactions; D015551:Autoimmunity / Q000276:immunology; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000494:pharmacology*; D015658:HIV Infections / Q000097:blood; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000494:pharmacology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009500:Neutralization Tests; D014771:Virion / Q000737:chemistry / Q000276:immunology
D000906:Antibodies; D000914:Antibodies, Viral; D006649:Histocompatibility Antigens; D007519:Isoantigens; D003165:Complement System Proteins