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
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U2 - 10.1002/eji.1830230423
DO - 10.1002/eji.1830230423
M3 - Article
C2 - 8458377
AN - SCOPUS:0027340041
SN - 0014-2980
VL - 23
SP - 917
EP - 921
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -