Replacement of the DR alpha chain with the E alpha chain enhances presentation of Mycoplasma arthritidis superantigen by the human class II DR molecule.
Mycoplasma arthritidis mitogen (MAM) is produced by an organism which can cause chronic proliferative arthritis in rodents. MAM possesses a typical superantigenic activity; it has the ability to activate a large panel of T cells which express specific V beta segments of the T-cell receptor. The presentation of MAM to T cells by antigen-presenting cells is mediated primarily through its binding to the major histocompatibility complex (MHC) class II E alpha chain in mice and the DR alpha chain in humans. However, MAM is much less active for human peripheral blood lymphocytes than for mouse splenocytes. It was suggested that a difference in MAM binding affinity between human and mouse class II molecules may account for their different MAM activities. To examine this possibility, we generated a panel of B-cell transfectants whose DR molecule is composed of either the DR alpha or the E alpha chain paired with a DR3 beta chain. The ability of these transfectants to present MAM to human peripheral T cells was analyzed. Our data show that transfectants expressing E alpha DR beta chimeric molecules have higher MAM-presenting activity than transfectants expressing wild-type DR alpha DR beta molecules, while the latter have higher activity in stimulating DR3-alloreactive T cells. Since both types of transfectants present MAM to T cells expressing the same T-cell receptor V beta gene families, the higher MAM-presenting activity of the E alpha transfectant is not due to its ability to interact with a different set of T cells. Furthermore, both the E alpha 1 and E alpha 2 domains contribute to this increased affinity for MAM binding. Taken together, our data suggest that there may be multiple MAM binding sites on the E alpha and DR alpha chains and residues unique to the E alpha chain may provide additional affinity for MAM.
Sawada
T
T
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030, USA.
Pergolizzi
R
R
Ito
K
K
Silver
J
J
Atkin
C
C
Cole
B C
BC
Chang
M D
MD
D017951:Antigen Presentation; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D006684:HLA-DR Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009174:Mycoplasma / Q000276:immunology*; D018089:Superantigens / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D006684:HLA-DR Antigens; D018089:Superantigens