Interaction of interleukin-2 (IL-2) mutant proteins with interleukin-2 receptors
Conference
·
· Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6029116
The authors have previously produced several human IL-2 mutant proteins by site specific mutagenesis. Deletion or substitution of alanine for cysteine at positions 58 and 105 results in the decrease of biological activities. Substitution of serine for cysteine at position 125 does not affect the activity, however, deletion of this cysteine or amino acids in its vicinity causes a dramatic loss of activity. In this study, the interaction of these mutant proteins with IL-2 receptors has been analyzed by evaluating the competition between these mutant proteins and recombinant DNA derived IL-2 (rIL-2) for the binding to murine CTLL-2, an IL-2 dependent cell line. Addition of unlabeled rIL-2 (1 x 10/sup -11/ to 10/sup -7/M) inhibited the binding of I/sup 125/-labeled rIL-2 (1 x 10/sup -10/M, specific activity 39.6 uCi/mg) to CTLL-2 cells in a concentration dependent manner. Mutant proteins with substitution of alanine for cysteine at position 58 (Ala 58) or deletion of cysteine at position 125 (Des-Cys 125) required a 100-fold higher concentration than rIL-2 to reach 50% inhibition. These results indicate that the decrease of biological activity in mutant proteins is partly, if not primarily, due to the attenuation in their abilities to bind IL-2 receptors.
- Research Organization:
- Federal Dept. of Agriculture, Bethesda, MD
- OSTI ID:
- 6029116
- Report Number(s):
- CONF-870644-
- Conference Information:
- Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
DAYS LIVING RADIOISOTOPES
DNA
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LYMPHOKINES
MAMMALS
MAN
MEMBRANE PROTEINS
MICE
MITOGENS
MUTANTS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RECOMBINANT DNA
RODENTS
TRACER TECHNIQUES
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
DAYS LIVING RADIOISOTOPES
DNA
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LYMPHOKINES
MAMMALS
MAN
MEMBRANE PROTEINS
MICE
MITOGENS
MUTANTS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RECOMBINANT DNA
RODENTS
TRACER TECHNIQUES
VERTEBRATES