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Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules

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Abstract

The ubiquitously expressed amyloid precursor-like protein 2 (APLP2) has been previously found to regulate cell surface expression of the major histocompatibility complex (MHC) class I molecule Kd and bind strongly to Kd. In the study reported here, we demonstrated that APLP2 binds, in varied degrees, to several other mouse MHC class I allotypes and that the ability of APLP2 to affect cell surface expression of an MHC class I molecule is not limited to Kd. Ld, like Kd, was found associated with APLP2 in the Golgi, but Kd was also associated with APLP2 within intracellular vesicular structures. We also investigated the effect of β2m on APLP2/MHC interaction and found that human β2m transfection increased the association of APLP2 with mouse MHC class I molecules, likely by affecting H2 class I heavy chain conformation. APLP2 was demonstrated to bind specifically to the conformation of Ld having folded outer domains, consistent with our previous results with Kd and indicating APLP2 interacts with the α1α2 region on each of these H2 class I molecules. Furthermore, we observed that binding to APLP2 involved the MHC α3/transmembrane/cytoplasmic region, suggesting that conserved as well as polymorphic regions of the H2 class I molecule may participate in interaction with APLP2. In summary, we demonstrated that APLP2’s binding, co-localization pattern, and functional impact vary among H2 class I molecules and that APLP2/MHC association is influenced by multiple domains of the MHC class I heavy chain and by β2m’s effects on the conformation of the heavy chain.

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Acknowledgments

This work was supported by National Institutes of Health Grant GM57428 (to J.C.S.) and GM74876 (to S.C.), UNMC Graduate Studies Fellowships (to A.T. and M.S.), and a Nebraska Center for Cellular Signaling Fellowship (to M.S.). We thank Dr. Ted Hansen, Dr. Wendy Maury, and Dr. Eric Long for gifts of antibodies, cell lines, and cloning vectors. We also gratefully acknowledge the assistance of Haley Capek, Vivek Gautam, Mary McIlhaney, and the personnel of the University of Nebraska Medical Center Cell Analysis Facility and Monoclonal Antibody Facility.

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Authors and Affiliations

  1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Amit Tuli & Joyce C. Solheim

  2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Mahak Sharma, Naava Naslavsky & Steve Caplan

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  1. Amit Tuli
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  2. Mahak Sharma
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  3. Naava Naslavsky
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Correspondence to Joyce C. Solheim.

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Tuli, A., Sharma, M., Naslavsky, N. et al. Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules. Immunogenetics 60, 303–313 (2008). https://doi.org/10.1007/s00251-008-0296-0

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