Enhanced activation ofhumanT cell clones specific forvirus-like particles expressing theHIVV3loopinthepresenceofHIVV3loop-specific polyclonal antibodies

SUMMARY Recombinant virus-like particles (VLP), formedbytheyeastTyplprotein, carrying theHIV gpl20V3loopon their surface (V3-VLP) havebeentested invitro forimmunogenicity and antigenicity byusing VLPp1-specific humanCD4+Tcell lines andclones. VLP-specific humanT celllines andclones were generated fromnormalindividuals, indicating thatVLP-specific precursorcells present intheperipheral lymphocyte poolcan beinduced toexpandclonally upon antigen challenge invitro, intheabsence ofprevious immunization. Itwas alsoshownthat V3-specific polyclonal antibodies enhance V3-VLP-induced activation ofVLP-specific T cell clones. Antibody-dependent potentiation hasbeenshownpreviously inotherantigen systems, anditdepends on enhanced uptakeofcomplexed antigen byFcreceptor-positive antigenpresenting cells. Since inthis caseantigen isinternalized bypresenting cells as acomplex, itcan beinferred that a similar eventofantibody-mediated antigen uptake can takeplace withV3specific Bcells, resulting inpresentation bytheBcells ofThelper epitopes derived fromprocessing oftheVLPp1 moiety. Thissuggests that Thelper cells specific forthecarrier VLP p1 protein can beactivated toprovide helptoV3-specific B cells inthepresenceoftheappropriate antigen construct.