The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells.

Abstract

There are at least two interleukin 2 (IL-2) binding peptides: one is the Mr 55,000 peptide (p55) reactive with the anti-Tac monoclonal antibody, and the other is a Mr 75,000 non-Tac IL-2 binding peptide (p75). Independently existing Tac or p75 peptides represent low-affinity IL-2 receptors, whereas high-affinity IL-2 receptors are expressed when both peptides are present and associated in a receptor complex. It has long been known that normal large granular lymphocytes (LGL) or leukemic cells from the patients with abnormal expansions of LGL can be activated by IL-2 not only to more-potent natural killer cells but also to effectors of lymphokine-activated killer (LAK) activity, although they do not express the Tac peptide. In the present study, using crosslinking methodology, we found that normal LGL and leukemic LGL from all individuals tested expressed the p75 IL-2 binding peptide but did not express the Tac peptide. These LGL leukemia cells made proliferative responses to IL-2 but required a much higher concentration than that required for the proliferation of normal phytohemagglutinin-stimulated T lymphoblasts that express high-affinity receptors. Furthermore, the addition of IL-2 to Tac-negative LGL leukemic cells augmented transcription of the Tac gene and induced the Tac peptide. Neither the IL-2-induced proliferation nor the upregulation of Tac gene expression was inhibited by the addition of anti-Tac. These results strongly suggest that the p75 peptide is responsible for IL-2-induced activation of LGL and that the p75 peptide alone can mediate an IL-2 signal. Thus, the p75 peptide may play an important role in the IL-2-mediated immune response not only by participating with the Tac peptide in the formation of the high-affinity receptor complex on T cells but also by contributing to the initial triggering of LGL activation so that these cells become efficient natural killer and lymphokine-activated killer cells.

Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats.

“…Although a minor population of non-T cells has been demonstrated to contain either the low-affinity IL-2R (38)(39)(40) or the intermediate-affinity (p70) IL-2R (41)(42)(43), the pivotal acquisition by the T cell of the high affinity (p55/p70) IL-2R is virtually synonymous with T-cell activation and may be essentially restricted to these cells. This would offer a further margin-of therapeutic specificity in terms of dosage optimization, since the cells bearing the high-affinity receptor could be targeted preferentially.…”

Leukemic CD3+ LGL share functional properties with their CD8+CD57+ cell counterpart expanded after BMT

“…12,13,37 In addition, we show here, by using BrdU incorporation, that a 3 day rhIL-2 stimulation induced a better proliferation of CD8 + CD57 + leukemic LGL than their CD8 + CD57 − cell counterpart. The disappearance of the CD57 expression on a longer time scale after 2 weeks is in accordance with the previously described impossibility for CD8 + CD3 + leukemic cells to retain the CD57 phenotype in long-term culture for up to 2 months.…”

“…The constitutively expressed p75 can form a high affinity receptor when p55 is upregulated upon IL-2 activation. 37 We first observed in short-term (day 3) in vitro cultures of LGL a 7-to 36-fold enhancement in stimulation indexes of 3 H-thymidine incorporation in the presence of increasing concentrations of exogenous rhIL-2 ranging from 20 to 100 U/ml (data not shown). The heterogeneity of the leukemic LGL described above with regards to the CD57 expression raised the question of the LGL subset involved in such dose-dependent rhIL-2 induced proliferation.…”

IL-1 and IL-4 as reciprocal regulators of IL-2 induced lymphocyte cytotoxicity

“…Differences in timing might explain the apparently divergent results with anti-CD25 antibodies which have been found to have either no effect on LAK induction (Tsudo et al, 1987) or to cause a partial blocking of LAK induction (Grimm et al, 1983;Shau et al, 1988). While the inhibition of LAK cytotoxicity by anti-CD25 is often marginal and much less pronounced than the inhibition of IL-2 induced lymphocyte proliferation (Siegel et al, 1987), the combination of anti-CD25 and antibodies specific for IL-2R-beta chain caused much greater inhibition of LAK than the latter alone (Phillips et al, 1989).…”