The MHC class II cofactor HLA-DM interacts with Ig in B cells

Henriette Macmillan, Michael J. Strohman, Sashi Ayyangar, Wei Jiang, Narendiran Rajasekaran, Armin Spura, Ann Hessell, Anne Marie Madec, Elizabeth D. Mellins

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.

    Original languageEnglish (US)
    Pages (from-to)2641-2650
    Number of pages10
    JournalJournal of Immunology
    Volume193
    Issue number6
    DOIs
    StatePublished - Sep 15 2014

    Fingerprint

    B-Lymphocytes
    Endosomes
    Peptides
    Endocytosis
    Antigen-Antibody Complex
    Polysaccharides
    Cell Line
    Proteins

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    Macmillan, H., Strohman, M. J., Ayyangar, S., Jiang, W., Rajasekaran, N., Spura, A., ... Mellins, E. D. (2014). The MHC class II cofactor HLA-DM interacts with Ig in B cells. Journal of Immunology, 193(6), 2641-2650. https://doi.org/10.4049/jimmunol.1400075

    The MHC class II cofactor HLA-DM interacts with Ig in B cells. / Macmillan, Henriette; Strohman, Michael J.; Ayyangar, Sashi; Jiang, Wei; Rajasekaran, Narendiran; Spura, Armin; Hessell, Ann; Madec, Anne Marie; Mellins, Elizabeth D.

    In: Journal of Immunology, Vol. 193, No. 6, 15.09.2014, p. 2641-2650.

    Research output: Contribution to journalArticle

    Macmillan, H, Strohman, MJ, Ayyangar, S, Jiang, W, Rajasekaran, N, Spura, A, Hessell, A, Madec, AM & Mellins, ED 2014, 'The MHC class II cofactor HLA-DM interacts with Ig in B cells', Journal of Immunology, vol. 193, no. 6, pp. 2641-2650. https://doi.org/10.4049/jimmunol.1400075
    Macmillan H, Strohman MJ, Ayyangar S, Jiang W, Rajasekaran N, Spura A et al. The MHC class II cofactor HLA-DM interacts with Ig in B cells. Journal of Immunology. 2014 Sep 15;193(6):2641-2650. https://doi.org/10.4049/jimmunol.1400075
    Macmillan, Henriette ; Strohman, Michael J. ; Ayyangar, Sashi ; Jiang, Wei ; Rajasekaran, Narendiran ; Spura, Armin ; Hessell, Ann ; Madec, Anne Marie ; Mellins, Elizabeth D. / The MHC class II cofactor HLA-DM interacts with Ig in B cells. In: Journal of Immunology. 2014 ; Vol. 193, No. 6. pp. 2641-2650.
    @article{d8d47cd759c44f31b4be86b3a3d2dfae,
    title = "The MHC class II cofactor HLA-DM interacts with Ig in B cells",
    abstract = "B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.",
    author = "Henriette Macmillan and Strohman, {Michael J.} and Sashi Ayyangar and Wei Jiang and Narendiran Rajasekaran and Armin Spura and Ann Hessell and Madec, {Anne Marie} and Mellins, {Elizabeth D.}",
    year = "2014",
    month = "9",
    day = "15",
    doi = "10.4049/jimmunol.1400075",
    language = "English (US)",
    volume = "193",
    pages = "2641--2650",
    journal = "Journal of Immunology",
    issn = "0022-1767",
    publisher = "American Association of Immunologists",
    number = "6",

    }

    TY - JOUR

    T1 - The MHC class II cofactor HLA-DM interacts with Ig in B cells

    AU - Macmillan, Henriette

    AU - Strohman, Michael J.

    AU - Ayyangar, Sashi

    AU - Jiang, Wei

    AU - Rajasekaran, Narendiran

    AU - Spura, Armin

    AU - Hessell, Ann

    AU - Madec, Anne Marie

    AU - Mellins, Elizabeth D.

    PY - 2014/9/15

    Y1 - 2014/9/15

    N2 - B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.

    AB - B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.

    UR - http://www.scopus.com/inward/record.url?scp=84921689789&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84921689789&partnerID=8YFLogxK

    U2 - 10.4049/jimmunol.1400075

    DO - 10.4049/jimmunol.1400075

    M3 - Article

    C2 - 25098292

    AN - SCOPUS:84921689789

    VL - 193

    SP - 2641

    EP - 2650

    JO - Journal of Immunology

    JF - Journal of Immunology

    SN - 0022-1767

    IS - 6

    ER -