MULTIPLE CTL SPECIFICITIES AGAINST AUTOLOGOUS HIV-1-INFECTED BLCLS

The cellular immune response to HIV-1 has been well studied but, in ma ny respects, remains incompletely defined. Although CTL specificities against highly conserved HIV-1 determinants as dictated by vaccinia/HI V-1 vector constructs have been described, much less is known regardin g patient cellular reactivities against autologous cells infected with HIV-1. One of the main obstacles in characterizing this cellular reac tivity has been the absence of a targeting system which accurately rep resents the HIV infected cell in vivo and is, at the same time, adapta ble for in vitro assays. Through the use of two separate strategies ai med at increasing cellular CD4 expression, we were able to infect B-ly mphocyte cell lines (BLCLs) with multiple strains of HIV-1. HIV-1-infe cted BLCLs were recognized by autologous effector cells with cytolytic specificities against env, gag, or pol determinants. In addition, HIV -1-infected BLCLs were capable of eliciting in vitro CTL reactivities directed against env-, gag-, and pol-expressing targets. This cellular reactivity was mediated by CD8(+) cells and was MHC Class I restricte d, suggesting a classical CTL response. Since multiple antigens are re cognized, an HIV-1-infected BLCL is a more natural representation of a n in vivo cellular target than other available testing systems and sho uld permit a more representative analysis of CTL responses during infe ction or following vaccination. (C) 1995 Academic Press, Inc.