AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 8, Number 5, 1992 Mary Ann Liebert, Inc., Publishers
Class II
(I-Ad) Restricted T-Cell Recognition of the V3 Loop Region of HIV-l gp!20
ANDREW P. WARREN and D. BRIAN THOMAS
ABSTRACT
CD4+ and gpl20-specific T-cell line, and subclone, were established from BALB/c mice following immunization with recombinant gp 120, using an adjuvant formulation (alum) acceptable for use in the human. The recognition specificity was determined against a panel of synthetic peptides corresponding to the primary sequence of the HXB2 strain of human immunodeficiency virus (HIV). An epitope was identified, corresponding to amino acid residues 322-341, and a further series of truncated peptides established the minimum determinant to be 327-341. Possible reasons for the immunodominance of the V, loop, and adjacent regions, for both antibody and T-cell recognition are discussed. A
INTRODUCTION
A ficiency
MAJOR NEUTRALIZING DETERMINANT of human immunode-
virus type 1 (HIV-1) is within the third hypervariregion of the envelope (env) glycoprotein, gpl20, referred to as the V3 loop, and antibodies to this region are specific for '~5 closely related virus isolates. Antibody specificity for recombinant proteins and synthetic peptides has mapped the determinant(s) to within the putative disulfide crosslinked loop between cysteine residues 296 and 331. Amino acid residues within the V, loop differ significantly between various strains of HIV-1 while the tip of the loop is highly conserved and contains the sequence GPGR (residues 312-315). The variable regions that Hank this conserved tip are considered to be the recognition sites for neutralizing antibodies and antipeptide antibodies are found able
to be virus variant
specific.6
Antigenic variation in env is a formidable problem for vaccination strategies, therefore, information on T-cell recognition specificity for conserved versus variable regions is of particular relevance to the development of recombinant and synthetic vaccines. To this end, there have been two approaches to identify T-cell epitopes. First, in humans, studies have been
National Institute for Medical Research, The
Ridgeway,
made on the T-cell responses to synthetic peptides (of seropositive individuals) following natural HIV infection or after immunization of normal healthy individuals with a recombinant vaccinia virus (VACC-
Class II
(I-Ad) Restricted T-Cell Recognition of the V3 Loop Region of HIV-l gp!20
ANDREW P. WARREN and D. BRIAN THOMAS
ABSTRACT
CD4+ and gpl20-specific T-cell line, and subclone, were established from BALB/c mice following immunization with recombinant gp 120, using an adjuvant formulation (alum) acceptable for use in the human. The recognition specificity was determined against a panel of synthetic peptides corresponding to the primary sequence of the HXB2 strain of human immunodeficiency virus (HIV). An epitope was identified, corresponding to amino acid residues 322-341, and a further series of truncated peptides established the minimum determinant to be 327-341. Possible reasons for the immunodominance of the V, loop, and adjacent regions, for both antibody and T-cell recognition are discussed. A
INTRODUCTION
A ficiency
MAJOR NEUTRALIZING DETERMINANT of human immunode-
virus type 1 (HIV-1) is within the third hypervariregion of the envelope (env) glycoprotein, gpl20, referred to as the V3 loop, and antibodies to this region are specific for '~5 closely related virus isolates. Antibody specificity for recombinant proteins and synthetic peptides has mapped the determinant(s) to within the putative disulfide crosslinked loop between cysteine residues 296 and 331. Amino acid residues within the V, loop differ significantly between various strains of HIV-1 while the tip of the loop is highly conserved and contains the sequence GPGR (residues 312-315). The variable regions that Hank this conserved tip are considered to be the recognition sites for neutralizing antibodies and antipeptide antibodies are found able
to be virus variant
specific.6
Antigenic variation in env is a formidable problem for vaccination strategies, therefore, information on T-cell recognition specificity for conserved versus variable regions is of particular relevance to the development of recombinant and synthetic vaccines. To this end, there have been two approaches to identify T-cell epitopes. First, in humans, studies have been
National Institute for Medical Research, The
Ridgeway,
made on the T-cell responses to synthetic peptides (of seropositive individuals) following natural HIV infection or after immunization of normal healthy individuals with a recombinant vaccinia virus (VACC-
