The superantigen staphylococcal enterotoxin A (SEA) and monoclonal antibody L243 share a common epitope but differ in their ability to induce apoptosis via MHC-II.
Crosslinking of MHC class II (MHC-II) molecules by antibodies or by superantigens (SAg) induces a variety of functional responses in the antigen presenting cell. We were able to allocate K39 as the residue that is essential for binding of antibody L243 to the alpha chain of HLA-DR. K39 is also essential for binding of staphylococcal enterotoxin A (SEA). However, the functional responses of the two ligands differ considerably exemplified by the ability of L243 to induce apoptosis in monocytic cells and in B cells, whereas SEA is unable to activate the apoptosis pathway. Despite the differences in functional responses, both ligands induce cell aggregation in MonoMac-1 cells. The SEA molecule with its two different binding sites associates one MHC alpha chain with one beta chain as opposed to two alpha chains that are brought into close proximity by the two identical antigen binding sites of L243. We therefore conclude that the spatial orientation of dimerized MHC-II and their associated proteins is an important factor for the nature of the transduced signal and consequently the outcome of functional responses.
Gross
Ulrike
U
Institute of Immunology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany.
Schroder
Anja K
AK
Haylett
Romney S
RS
Arlt
Sabine
S
Rink
Lothar
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004768:Enterotoxins / Q000032:analysis* / Q000276:immunology; D000939:Epitopes / Q000032:analysis* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D051379:Mice; D018089:Superantigens / Q000032:analysis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal