Induction of a major histocompatibility complex class I-restricted cytotoxic T-lymphocyte response to a highly conserved region of human immunodeficiency virus type 1 (HIV-1) gp120 in seronegative humans immunized with a candidate HIV-1 vaccine.
Efforts to induce broadly reactive immunity against human immunodeficiency virus type 1 (HIV-1) have been impaired by the extent of sequence variation exhibited by this lentivirus. Cytotoxic T lymphocytes (CTL) specific for other viruses such as influenza virus have been shown to mediate immunity against divergent viral strains, a property that is related to the ability of CTL to recognize processed antigen derived from conserved viral proteins. A recent candidate HIV-1 vaccine regimen has been described in which subjects receive a primary immunization with a recombinant vaccinia virus expressing gp160 and then a booster immunization with recombinant gp160. Volunteers immunized with this regimen have exhibited augmented humoral responses and have also developed CD4+ and CD8+ CTL specific for gp160. In this report, we have identified the epitopes recognized by CD4+ and CD8+ CTL obtained from two vaccines. An immunodominant CD8+ CTL response was HLA-A3.1 restricted and recognized a 10-amino-acid epitope (gp120/38-47) in a highly conserved region of gp120. CTL specific for the epitope gp120/38-47 were able to lyse targets sensitized with peptides corresponding to all known natural sequence variants in this region. In addition, other HLA class I-restricted CTL epitopes were identified in relatively conserved regions of gp120 and gp41, and CD4+ CTL were shown to recognize two different regions of gp120. Thus, in these two volunteers, immunization with a single strain of HIV-1 induced CD4+ and CD8+ CTL that are specific for multiple conserved regions of HIV-1 and would be expected to recognize a broad range of viral isolates.
Johnson
R P
RP
Infectious Disease Unit, Massachusetts General Hospital, Charlestown 02129.
Hammond
S A
SA
Trocha
A
A
Siliciano
R F
RF
Walker
B D
BD
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002986:Clinical Trials as Topic; D002999:Clone Cells / Q000276:immunology; D017124:Conserved Sequence / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D018023:HIV Seronegativity; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015791:HLA-A3 Antigen; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016915:AIDS Vaccines; D016827:CD8 Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D015234:HLA-A Antigens; C071694:HLA-A*03:01:01:01 antigen; D015791:HLA-A3 Antigen; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D011498:Protein Precursors