Mutation of Asp20 of human interleukin-2 reveals a dual role of the p55 α chain of the interleukin-2 receptor

Claudia L. Flemming, Stephen J Russell, Mary K L Collins

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mutation of Asp20 in human interleukin-2 (IL-2) to Lys is known to result in an IL-2 molecule with unchanged binding to the p55 subunit of the IL-2 receptor, but with greatly decreased affinity for the p75 subunit (Collins, L., Tsien, W.-H., Seals, C. et al. Proc. Natl. Acad. Sci USA 1988. 85: 7709). Here we demonstrate that Lys20 IL-2 competed with a reduced (10-fold) affinity for high-affinity IL-2 receptors on two murine cell lines HT2 and CTLL. In parallel with this difference in receptor interaction, Lys20 IL-2 stimulated half-maximal HT2 cell proliferation at a 10-fold higher concentration than wild-type IL-2. However, half-maximal stimulation of CTLL cells required a 100-fold higher concentration of Lys20 IL-2. A similar 100-fold reduction in bioactivity of Lys20 IL-2 was observed for primary, activated, human or murine lymphocytes. Anti-p55 antibodies increased the concentration of Lys20 IL-2 required to stimulate HT2 cells to that required for CTLL cells. These data suggest that CTLL cells, while able to bind Lys20 IL-2 with high affinity, are lacking a p55-dependent function necessary for optimal stimulation. Therefore, p55 has a dual role, being important both for high-affinity IL-2 binding and for optimal cell triggering.

Original languageEnglish (US)
Pages (from-to)917-921
Number of pages5
JournalEuropean Journal of Immunology
Volume23
Issue number4
StatePublished - Apr 1993
Externally publishedYes

Fingerprint

Interleukin-2 Receptors
Interleukin-2
Mutation
Anti-Idiotypic Antibodies
Cell Proliferation
Lymphocytes
Cell Line

Keywords

  • Interleukin-2
  • Mutational analysis
  • Receptor

ASJC Scopus subject areas

  • Immunology

Cite this

Mutation of Asp20 of human interleukin-2 reveals a dual role of the p55 α chain of the interleukin-2 receptor. / Flemming, Claudia L.; Russell, Stephen J; Collins, Mary K L.

In: European Journal of Immunology, Vol. 23, No. 4, 04.1993, p. 917-921.

Research output: Contribution to journalArticle

@article{4712be6a04c34f609b57f93c3cac066d,
title = "Mutation of Asp20 of human interleukin-2 reveals a dual role of the p55 α chain of the interleukin-2 receptor",
abstract = "Mutation of Asp20 in human interleukin-2 (IL-2) to Lys is known to result in an IL-2 molecule with unchanged binding to the p55 subunit of the IL-2 receptor, but with greatly decreased affinity for the p75 subunit (Collins, L., Tsien, W.-H., Seals, C. et al. Proc. Natl. Acad. Sci USA 1988. 85: 7709). Here we demonstrate that Lys20 IL-2 competed with a reduced (10-fold) affinity for high-affinity IL-2 receptors on two murine cell lines HT2 and CTLL. In parallel with this difference in receptor interaction, Lys20 IL-2 stimulated half-maximal HT2 cell proliferation at a 10-fold higher concentration than wild-type IL-2. However, half-maximal stimulation of CTLL cells required a 100-fold higher concentration of Lys20 IL-2. A similar 100-fold reduction in bioactivity of Lys20 IL-2 was observed for primary, activated, human or murine lymphocytes. Anti-p55 antibodies increased the concentration of Lys20 IL-2 required to stimulate HT2 cells to that required for CTLL cells. These data suggest that CTLL cells, while able to bind Lys20 IL-2 with high affinity, are lacking a p55-dependent function necessary for optimal stimulation. Therefore, p55 has a dual role, being important both for high-affinity IL-2 binding and for optimal cell triggering.",
keywords = "Interleukin-2, Mutational analysis, Receptor",
author = "Flemming, {Claudia L.} and Russell, {Stephen J} and Collins, {Mary K L}",
year = "1993",
month = "4",
language = "English (US)",
volume = "23",
pages = "917--921",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "4",

}

TY - JOUR

T1 - Mutation of Asp20 of human interleukin-2 reveals a dual role of the p55 α chain of the interleukin-2 receptor

AU - Flemming, Claudia L.

AU - Russell, Stephen J

AU - Collins, Mary K L

PY - 1993/4

Y1 - 1993/4

N2 - Mutation of Asp20 in human interleukin-2 (IL-2) to Lys is known to result in an IL-2 molecule with unchanged binding to the p55 subunit of the IL-2 receptor, but with greatly decreased affinity for the p75 subunit (Collins, L., Tsien, W.-H., Seals, C. et al. Proc. Natl. Acad. Sci USA 1988. 85: 7709). Here we demonstrate that Lys20 IL-2 competed with a reduced (10-fold) affinity for high-affinity IL-2 receptors on two murine cell lines HT2 and CTLL. In parallel with this difference in receptor interaction, Lys20 IL-2 stimulated half-maximal HT2 cell proliferation at a 10-fold higher concentration than wild-type IL-2. However, half-maximal stimulation of CTLL cells required a 100-fold higher concentration of Lys20 IL-2. A similar 100-fold reduction in bioactivity of Lys20 IL-2 was observed for primary, activated, human or murine lymphocytes. Anti-p55 antibodies increased the concentration of Lys20 IL-2 required to stimulate HT2 cells to that required for CTLL cells. These data suggest that CTLL cells, while able to bind Lys20 IL-2 with high affinity, are lacking a p55-dependent function necessary for optimal stimulation. Therefore, p55 has a dual role, being important both for high-affinity IL-2 binding and for optimal cell triggering.

AB - Mutation of Asp20 in human interleukin-2 (IL-2) to Lys is known to result in an IL-2 molecule with unchanged binding to the p55 subunit of the IL-2 receptor, but with greatly decreased affinity for the p75 subunit (Collins, L., Tsien, W.-H., Seals, C. et al. Proc. Natl. Acad. Sci USA 1988. 85: 7709). Here we demonstrate that Lys20 IL-2 competed with a reduced (10-fold) affinity for high-affinity IL-2 receptors on two murine cell lines HT2 and CTLL. In parallel with this difference in receptor interaction, Lys20 IL-2 stimulated half-maximal HT2 cell proliferation at a 10-fold higher concentration than wild-type IL-2. However, half-maximal stimulation of CTLL cells required a 100-fold higher concentration of Lys20 IL-2. A similar 100-fold reduction in bioactivity of Lys20 IL-2 was observed for primary, activated, human or murine lymphocytes. Anti-p55 antibodies increased the concentration of Lys20 IL-2 required to stimulate HT2 cells to that required for CTLL cells. These data suggest that CTLL cells, while able to bind Lys20 IL-2 with high affinity, are lacking a p55-dependent function necessary for optimal stimulation. Therefore, p55 has a dual role, being important both for high-affinity IL-2 binding and for optimal cell triggering.

KW - Interleukin-2

KW - Mutational analysis

KW - Receptor

UR - http://www.scopus.com/inward/record.url?scp=0027340041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027340041&partnerID=8YFLogxK

M3 - Article

C2 - 8458377

AN - SCOPUS:0027340041

VL - 23

SP - 917

EP - 921

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 4

ER -