Abstract
Dimerization of class II major histocompatibility complex (MHC) plays an important role in the MHC biological function. Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing specific T cell receptor Vbeta elements. Here we have used structural, sedimentation, and surface plasmon resonance detection approaches to investigate the molecular interactions between MAM and the class II MHC molecule HLA-DR1 in the context of a hemagglutinin peptide-(306-318) (HA). Our results revealed that zinc ion can efficiently induce the dimerization of the HLA-DR1/HA complex. Because the crystal structure of the MAM/HLA-DR1/hemagglutinin complex in the presence of EDTA is nearly identical to the structure of the complex crystallized in the presence of zinc ion, Zn(2+) is evidently not directly involved in the binding between MAM and HLA-DR1. Sedimentation and surface plasmon resonance studies further revealed that MAM binds the HLA-DR1/HA complex with high affinity in a 1:1 stoichiometry, in the absence of Zn(2+). However, in the presence of Zn(2+), a dimerized MAM/HLA-DR1/HA complex can arise through the Zn(2+)-induced DR1 dimer. In the presence of Zn(2+), cooperative binding of MAM to the DR1 dimer was also observed.
Highlights
Major histocompatibility complex (MHC)3 molecules can present a wide variety of antigens to T lymphocytes
X-ray crystallographic analyses have indicated that class II MHC can further form a (␣)2 superdimer of the MHC heterodimer [2]
Dimerization of soluble class II MHC molecules has not been observed in solution, even under the extreme acidic conditions used for crystallization [1]
Summary
Major histocompatibility complex (MHC)3 molecules can present a wide variety of antigens to T lymphocytes. MAM Binds to the HLA-DR1/HA Complex with a 1:1 Stoichiometry, in the Absence of Zn2ϩ—To further investigate the molecular interaction between MAM and class II MHC molecule, we performed sedimentation velocity analytical ultracentrifugation with individual proteins and mixtures (Fig. 2). Because the running buffers for our SPR and equilibrium analyses contained excessive amounts of EDTA, our result clearly indicated that Zn2ϩ is not directly involved in the high affinity binding of MAM with class II MHC, the HLA-DR1/HA complex.
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