The alpha chain of the IL-2 receptor determines the species specificity of high-affinity IL-2 binding

被引:11
作者
Liu, KD
Greene, WC
Goldsmith, MA
机构
[1] UNIV CALIF SAN FRANCISCO,SCH MED,GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94141
[2] UNIV CALIF SAN FRANCISCO,SCH MED,DEPT MED,SAN FRANCISCO,CA 94143
[3] UNIV CALIF SAN FRANCISCO,SCH MED,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143
关键词
human; interleukin; 2; ligand binding; lymphocyte; mouse;
D O I
10.1006/cyto.1996.0082
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin 2 (IL-2) mediated signalling results from ligand binding and subsequent heterodimerization of IL-2r beta and gamma(c). The high-affinity IL-2 receptor (IL-2r) is a heterotrimer comprised of the IL-2r alpha, IL-2r beta and gamma(c) subunits. Whereas human IL-2 effectively binds to either human or murine lymphocytes, murine IL-2 binds with markedly higher affinity to murine receptor complexes than to human complexes, Using cell lines stably expressing heterotrimeric IL-2r that vary in the species origin of individual subunits, we have demonstrated that IL-2r alpha is primarily responsible for the species specificity of IL-2 binding, Studies of ligand binding to the low affinity receptor demonstrated that IL-2r alpha displays a similar species preference to the heterotrimeric complex, Moreover, differences in ligand binding are reflected in differences in proliferation, A cell line expressing human IL-2r alpha and IL-2r beta along with murine gamma(c) vigorously proliferated only in response to human IL-2 at low doses, while both human and murine IL-2 stimulated proliferation of a cell line containing murine IL-2r alpha (as well as human IL-2r beta and murine gamma(c)). Therefore, IL-2r alpha is the chain primarily responsible for the species specificity of ligand binding. (C) 1996 Academic Press Limited
引用
收藏
页码:613 / 621
页数:9
相关论文
共 35 条
[2]   UNRAVELING THE STRUCTURE OF IL-2 [J].
BAZAN, JF .
SCIENCE, 1992, 257 (5068) :410-412
[3]   SPECIES SPECIFICITY OF INTERLEUKIN-2 BINDING TO INDIVIDUAL RECEPTOR COMPONENTS [J].
COLLINS, MKL .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1989, 19 (08) :1517-1520
[4]   CLONING, SEQUENCE AND EXPRESSION OF HUMAN INTERLEUKIN-2 RECEPTOR [J].
COSMAN, D ;
CERRETTI, DP ;
LARSEN, A ;
PARK, L ;
MARCH, C ;
DOWER, S ;
GILLIS, S ;
URDAL, D .
NATURE, 1984, 312 (5996) :768-771
[5]  
EHLERS M, 1994, J IMMUNOL, V153, P1744
[6]  
FUNG MR, 1991, J IMMUNOL, V147, P1253
[7]   IDENTIFICATION AND CLONING OF A NOVEL IL-15 BINDING-PROTEIN THAT IS STRUCTURALLY RELATED TO THE ALPHA-CHAIN OF THE IL-2 RECEPTOR [J].
GIRI, JG ;
KUMAKI, S ;
AHDIEH, M ;
FRIEND, DJ ;
LOOMIS, A ;
SHANEBECK, K ;
DUBOSE, R ;
COSMAN, D ;
PARK, LS ;
ANDERSON, DM .
EMBO JOURNAL, 1995, 14 (15) :3654-3663
[8]   UTILIZATION OF THE BETA-CHAIN AND GAMMA-CHAIN OF THE IL-2 RECEPTOR BY THE NOVEL CYTOKINE-IL-15 [J].
GIRI, JG ;
AHDIEH, M ;
EISENMAN, J ;
SHANEBECK, K ;
GRABSTEIN, K ;
KUMAKI, S ;
NAMEN, A ;
PARK, LS ;
COSMAN, D ;
ANDERSON, D .
EMBO JOURNAL, 1994, 13 (12) :2822-2830
[9]  
GOLDSMITH MA, 1995, J IMMUNOL, V154, P2033
[10]  
GOLDSMITH MA, 1994, CYTOKINE HDB, P57