An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes.

Abstract

Because cytotoxic T lymphocytes (CTL) may be important for preventing direct cell-to-cell transmission of human immunodeficiency virus (HIV), the agent responsible for acquired immunodeficiency syndrome, we have begun to investigate the epitope specificity and immune response (Ir) gene control of anti-HIV CTL responses in experimental animals. Mice were infected with a recombinant vaccinia virus expressing the HIV gpl60 envelope gene, and the primed lymphocytes were restimulated in vitro with a transfected histocompatible cell line expressing the same gene. Our results show that H-2d mice are CTL high responders and H-2k mice are low responders to the HIV gpl60 envelope protein under these conditions. Moreover, the H-2d mice respond predominantly to a single immunodominant site represented by a 15-residue synthetic peptide conforming to the amphipathic a-helix model of T-cell epitopes and seen by CD4-CD8+ CTL in association with the Dd class I major histocompatibility complex (MHC) molecules. The facts that CTL responses were detected in the context of only one of four class I MHC molecules tested and that the response was limited predominantly to a single epitope indicate that the CTL repertoire elicited by the HIV envelope protein in association with murine class

Immunological reactivity of a human immunodeficiency virus type I derived peptide representing a consensus sequence of the GP 120 major neutralizing region V3

“…The isolated cells were restimulated for 7 days with the gp 120-IIIB recombinant vaccinia virus (2 x 107 PFU/cell). Target cells (p 815 mastozytoma cells) were incubated for 1 h with different concentrations of the peptides (10 gM, 0.1 gM, 1 nM) and tested in a 3 h cytolytic assay for SlCr-release using different target/effector-cell ratios [27].…”

“…A murine H2-D d restricted CTL-cell epitope is located in the V3 loop sequence of HIV-IIIB and has been characterized in its immunological properties (27)(28)(29). To confirm the functional conservation of this epitope in our V3-C36 peptide, recognition to V3-C36 derived peptides was tested in a 3 h cytolytic assay.…”

“…Further, a HIV-1/IIIB derived minimal peptide of gp 120/V3 was shown to be recognized as target for cellular immune response in BALB/c mice immunized with IIIB-env recombinant vaccinia virus [27][28][29]. CTLs raised against the IIIB-and against the MN-specific sequences by an env-recombinant vaccinia virus were completely not crossreactive.…”

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1IIIb and an O‐glycosylated analogue

“…In this report we compared the structures of a 15-residue peptide from the HIV-1IIIB V3 loop and a glycosylated analogue with N-acetylgalactosamine (NAG) c~-linked to the threonine four residues to the C-terminal side of the so-called immunodominant tip [18,19] (sequence -GPGR-) of the loop. As this peptide is also an immunodominant epitope for CTL recognition [20][21][22][23], we have also tested these peptides for their ability to be recognized by class I-MHC molecule-restricted CTL as measured by lysis of a tumor cell line incubated with the peptides.…”

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

“…All vectors contained a human codon-optimized gene encoding HIV-1 gp120 (syngp120); this gene was derived from the clade B MN strain of HIV-1, and included a V3 loop substitution from HIV-1 LAI, that introduced an immunodominant H2D d restricted V3 epitope (RGPGRAFVTI), recognized in BALB/c mice [37,38]. Three different HSVgp120 amplicon vectors and an E1-deleted, replication defective type 5 adenovirus (rAd5) vector were constructed.…”