CD99 costimulation up-regulates T cell receptor-mediated activation of JNK and AP-1.
Although CD28 is the principal T cell costimulatory molecule for the T cell receptor, a number of other cell surface proteins have costimulatory functions and perform specific roles in different contexts. Here we analyzed the mechanism of CD99 costimulation of the T cell receptor. Cooperation of CD99 engagement with suboptimal TCR/CD3 signals resulted in greatly enhanced CD4+ T cell proliferation. CD99 costimulation also led to elevated expression of CD25 and GM1 on the CD4+ T cell surface within 3 days. In Jurkat TAg cells, CD99 costimulation led to increased apoptosis compared to stimulation with CD3 or CD99 alone. CD99 costimulation also augmented activation of MAP kinases, especially of JNK, and increased AP-1 activation was also observed using a luciferase reporter assay. These results show that CD99 has a costimulatory function for T cells and acts by a mechanism distinct from CD28.
Yoon
Sang Soon
SS
Department of Pathology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Kim
Hyun Jung
HJ
Chung
Doo Hyun
DH
Kim
Tae Jin
TJ
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005677:G(M1) Ganglioside / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000235:genetics; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D018808:Transcription Factor AP-1; D005677:G(M1) Ganglioside; D048031:JNK Mitogen-Activated Protein Kinases