STUDIES ON IN-VIVO INDUCTION OF HIV-1 ENVELOPE-SPECIFIC CYTOTOXIC T-LYMPHOCYTES BY SYNTHETIC PEPTIDES FROM THE V3 LOOP REGION OF HIV-1 IIIBGP120

We have previously reported the induction of MHC class I-restricted, C D8(+) cytotoxic T lymphocytes (CTLs) specific to human immunodeficienc y virus type 1 (HIV-1) in mice by a 15-amino acid peptide (R15K) from the V3 loop in gp120, We now present evidence showing that CTL activit y induced by R15K was stable for 8-10 weeks after a single injection a nd that as little as 20 mu g peptide was sufficient for efficient CTL induction in vivo, While induction of CTLs was efficient with R15K emu lsified in either complete or incomplete Freund's adjuvant, only a low -level CTL response was observed in mice immunized with R15K in either alum or saline, We analyzed a series of carrier-free synthetic peptid es ranging in length from 8 to 24 amino acids from the V3 loop region and observed that peptide R1OI consisting of 10 amino acids from the m iddle portion of R15K was more efficient for CTL induction, Additional ly, lymph node cells from mice immunized with 24 and 15 amino acid pep tides (N24G and R15K, respectively) when restimulated in vitro with R1 OI exhibited greater HIV-1 env-specific CTL activity than when either of the longer peptides was used for restimulation, A peptide consistin g of only 8 amino acids (R8K) was sufficient neither for inducing prim ary CTLs nor for in vitro restimulation of lymph node CTL precursors, These results establish that a carrier-free 10-amino acid synthetic pe ptide from the V3 loop region in HIV-1 gp120 has the optimal sequence for efficient induction of HIV env-specific CTLs in mice, (C) 1995 Aca demic Press, Inc.