Induction of cytotoxic cell activity by peptide fragments of β2-microglobulin

Abstract

A heptapeptide fragment of β2-microglobulin has been described by Abiko in hemodialysates of uremic patients and found to inhibit E-rosette formation by hyman T cells. In order to study the possible immunoregulatory effects of this heptapeptide, we investigated its effect on human cytotoxic cell activity. Low concentrations (10−8 to 10−7 M) of the heptapeptide enhanced cytotoxic activity of human lymphocytes against herpes simplex virus-infected cells by 50–60% whereas higher concentrations (10−4M) depressed cytoxicity. When lymphocytes were incubated with the heptapeptide during an in vitro sensitization assay, an even stronger enhancement was observed. In an attempt to define possible structure-activity correlations, synthetic peptide fragments were also tested for their effect on cytotoxic cell activity. Thus, the corresponding desHis-hexapeptide (2–7) had little enhancing effect on fresh lymphocyte cytotoxicity but significantly enhanced cytotoxic activity following presensitization. In contrast, further amino acid deletions resulting in 3–7, 4–7, 5–7 or 6–7 fragments had no significant activity. Alternatively, C-terminal deletions resulting in 1–6, 1–5 or 1–4 fragments also failed to exert any effect on lymphocyte-mediated cytotoxicity. We suggest that the heptapeptide and its 2–7 hexapeptide fragment may play a role in regulating host cytotoxic responses to viruses in health and disease.