HIV UTILIZES "T CELL ANTAGONISM"

In HIV-1 infection, naturally occurring variants of the epitopes recognized by cytotoxic T lymphocytes may act as antagonists in vivo, as the corresponding peptides specifically prevent a CTL response directed against the virus in vitro, according to a report published in Nature (June 2).

In order to investigate this effect, researchers from the Nuffield department of clinical medicine and institute of molecular medicine, Oxford University, generated a number of CTL cell lines from infected individuals, specific for either p17-3, p24-13 or p24-14. The researchers demonstrated effective antagonism of CTL by variants at three epitopes. The mechanism of the antagonism seen here and in previous reports has not been explained, note the researchers. If antagonism results from a weak interaction between T-cell receptor and peptide, it may be overcome by increasing the concentration of agonist/antagonist peptides (so that the agonist effect outweighs the antagonist effect) or by increasing the time CTL's interact with targets.

In vitro, the presence of the antagonist prevents the T cell from performing its effector function, but does not turn it off. Although the mechanism is unknown, several non-mutually exclusive mechanisms have been proposed, said Paul Allen, department of pathology at Washington University, and Rolf Zinkernagel, institute of experimental immunology, University of Zurich, in an accompanying editorial. One proposal is that the non-stimulatory ligands play a passive role, diluting out stimulatory ligands; another is that antagonists actively deliver a negative signal upon TCR contact. The identification of highly-active antagonists, said Messrs Allen and Zinkernagel, would seem to favor the active model.