Identification of a costimulatory molecule rapidly induced by CD40L as CD44H.
The interaction between CD40 ligand and CD40 is critical for activation of T and B cells in vivo. We have recently demonstrated that this interaction rapidly induces a novel costimulatory activity distinct from B7 and independent of CD28. To study the molecular basis of the costimulatory activity, we have produced a novel monoclonal antibody, TM-1, that binds an 85-kilodalton costimulatory molecule rapidly induced by CD40L. Expression cloning reveals that TM-1 binds CD44H. CD44H expressed on Chinese hamster ovary cells has potent costimulatory activity for clonal expansion of T cells isolated from both wild-type mice and these with a targeted mutation of CD28. Thus, CD44H costimulates T cell proliferation by a CD28-independent mechanism. These results revealed that CD44H is a costimulatory molecule rapidly induced by CD40L.
Guo
Y
Y
Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center, New York 10016, USA.
Wu
Y
Y
Shinde
S
S
Sy
M S
MS
Aruffo
A
A
Liu
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand