Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation.
A successful immune response requires intercellular contact between T and B lymphocytes. We recently showed that CD28, a T cell surface protein that regulates an activation pathway, could mediate intercellular adhesion with activated B cells by interaction with the B7 antigen. Here we show that CD28 is the primary receptor for B7 on activated peripheral blood T cells, that CD28 binds to B7 in the absence of other accessory molecules, and that interaction between CD28 and B7 is costimulatory for T cell activation. To characterize the binding of CD28 to B7, we have produced genetic fusions of the extracellular portions of B7 and CD28, and immunoglobulin (Ig) C gamma 1 chains. 125I-labeled B7 Ig bound to CD28-transfected Chinese hamster ovary (CHO) cells, and to immobilized CD28 Ig with a Kd approximately 200 nM. B7 Ig also inhibited CD28-mediated cellular adhesion. The function of CD28-B7 interactions during T cell activation was investigated with soluble fusion proteins and with B7-transfected CHO cells. Immobilized B7 Ig and B7+ CHO cells costimulated T cell proliferation. Stimulation of T cells with B7+ CHO cells also specifically increased levels of interleukin 2 transcripts. These results demonstrate that the CD28 signaling pathway could be activated by B7, resulting in increased T cell cytokine production and T cell proliferation. Cellular interactions mediated by B7 and CD28 may represent an important component of the functional interactions between T and B lymphoid cells.
Linsley
P S
PS
Oncogen Division, Bristol-Myers-Squibb Pharmaceutical Research Institute, Seattle, Washington 91821.
Brady
W
W
Grosmaire
L
L
Aruffo
A
A
Damle
N K
NK
Ledbetter
J A
JA
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D007376:Interleukin-2; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4