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An HIV p24 heptapeptide down-regulates antigen-specific responses in vitro interfering at the level of the T3-Ti
A L Luzzati1, E Giacomini, L Giordani
1Department of Immunology, Istituto Superiore di Sanità, Rome, Italy.
Insights
A synthetic peptide from HIV p24, Ch7, is the shortest form that fully suppresses antigen-specific immune responses. It inhibits antibody induction and T-cell activation via the T3-Ti complex, offering insights into HIV-related immune defects.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Ch7 (RGSDIAG) is a synthetic heptapeptide derived from a conserved region of HIV p24 (amino acids 232-238).
- Previous studies demonstrated its ability to suppress antigen-induced responses in normal human peripheral blood lymphocytes (PBL).
Purpose of the Study:
- To determine the shortest effective peptide sequence of Ch7 for suppressing immune responses.
- To investigate the specificity of Ch7's inhibitory effects on different immune cell activation pathways.
Main Methods:
- Dose-dependent inhibition assays using specific antigens (sheep red cells, Candida albicans) and mitogens (PWM).
- Assessment of antibody induction and immunoglobulin-secreting cell counts.
- Evaluation of T-cell proliferation and activation markers (anti-CD3, anti-CD2).
Main Results:
- Ch7 was identified as the shortest peptide retaining full inhibitory capacity.
- The peptide dose-dependently inhibited specific antibody responses to SRC and Candida albicans.
- Ch7 inhibited anti-CD3-induced lymphoproliferation but did not affect anti-CD2 activation or PWM-stimulated immunoglobulin production.
Conclusions:
- A conserved HIV p24 epitope in Ch7 can prevent antigen-specific antibody induction by interfering with lymphocyte activation through the T3-Ti complex.
- These findings suggest a mechanism for abrogating immune functions defective in HIV-infected individuals.
Abstract:
Ch7 (RGSDIAG), a synthetic heptapeptide derived from a conserved region of HIV p24 (aa 232-238), was previously shown to suppress antigen-induced responses in cultures of normal human peripheral blood lymphocytes (PBL). We show in this paper that Ch7 is the shortest peptide retaining full inhibitory capacity. Further, the peptide inhibited efficiently and in a dose-dependent manner the induction of a specific antibody response to the antigens SRC (sheep red cells) and Candida albicans but did not exert any effect on the induction of immunoglobulin-secreting cells in PWM-stimulated cultures. Finally, Ch7 inhibited anti-CD3-induced lymphoproliferation but did not affect anti-CD2 activation. These results suggest that a conserved epitope of HIV p24 may be able to prevent the induction of antigen-specific antibody responses by interfering with lymphocyte activation via the T3-Ti complex, resulting in the abrogation of immune functions that are defective in HIV-infected individuals.
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