title: Replacement of the DR alpha chain with the E alpha chain enhances presentation of Mycoplasma arthritidis superantigen by the human class II DR molecule.
abstract: 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.
authors.affiliation: Department of Medicine, North Shore University Hospital, Manhasset, New York 11030, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sawada
authors.forename: R
authors.initials: R
authors.lastname: Pergolizzi
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: J
authors.initials: J
authors.lastname: Silver
authors.forename: C
authors.initials: C
authors.lastname: Atkin
authors.forename: B C
authors.initials: BC
authors.lastname: Cole
authors.forename: M D
authors.initials: MD
authors.lastname: Chang
mesh_terms: 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
chemical_list: D006684:HLA-DR Antigens; D018089:Superantigens