Induction of cytotoxic cell activity by peptide fragments of beta 2-microglobulin

A heptapeptide fragment of beta 2-microglobulin has been described by Abiko in hemodialysates of uremic patients and found to inhibit E-rosette formation by human 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(-4)M) depressed cytotoxicity. 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.