Expression and function of B7-1 (CD80) and B7-2 (CD86) on human epidermal Langerhans cells.
In addition to T cell receptor triggering, activation of T cells requires costimulatory signals that have been shown to be mainly initiated through CD28. We analyzed the expression and function of the two ligands for CD28, B7-1 (CD80) and B7-2 (CD86), on human Langerhans cells (LC), the antigen-presenting cells from epidermis. Human LC freshly isolated from epidermis (fLC) expressed significant level of B7-2, which was increased upon a short culture in vitro. In contrast, B7-1 was undetectable on fLC but appeared at the cell surface after a 3-day culture in vitro. Pre-incubation of 18-h cultured LC with anti-B7-2 monoclonal antibodies (mAB) was sufficient to abrogate the binding of CTLA4-Ig fusion protein, while a combination of both mAB against B7-1 and B7-2 was necessary to obtain a complete inhibition of CTLA4-Ig binding on 3-day cultured LC, showing the absence of a third CTLA4 ligand. The function of B7-1 and B7-2 on human LC has been analyzed by adding mAb at the beginning of mixed epidermal cell lymphocyte reactions. Anti-B7-2 mAb and CTLA4-Ig, but not anti-B7-1 mAb, strongly inhibited allogenic. as well as recall antigen-induced T cell proliferation supported by fLC or 3-day cultured LC. Collectively, these results demonstrate that B7-2 is the major ligand for CD28/CTLA4 at the LC surface and that it plays a crucial role in human LC co-stimulatory function with little, if any, dependence of B7-1 expression.
Rattis
F M
FM
Laboratorie Peau Humaine et Immunité, INSERM U346, Lyon, France.
Péguet-Navarro
J
J
Staquet
M J
MJ
Dezutter-Dambuyant
C
C
Courtellemont
P
P
Redziniak
G
G
Schmitt
D
D
D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis* / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000502:physiology*; D051940:B7-2 Antigen; D002469:Cell Separation; D002478:Cells, Cultured; D004817:Epidermis / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins