MHC class II proteins contain a potential binding site for the verotoxin receptor glycolipid CD77.
Globotriaosyl ceramide or CD77 functions as a cell surface receptor for toxins of the Shiga toxin/verotoxin family and as a marker for germinal center stage B-cells. The B-cell protein CD19 and the interferon-alpha receptor possess verotoxin-like amino acid sequences in their extracellular domains, and CD77 has been shown to function in CD19-mediated adhesion and interferon-induced growth inhibition. The Burkitt's lymphoma cell line, Daudi, is similar to germinal center B-cells in their expression of CD77, CD19 and MHC class II molecules. Using the multiple sequence alignment program, ClustalW, we have identified a verotoxin-like amino acid sequence on the beta-chain of human and murine MHC class II molecules. Binding of CD77 at this site could modulate the peptide-binding properties of these MHC class II molecules. Using Western blot analysis of whole cell extracts, we found that CD77-positive Daudi cells have higher levels of HLA-D proteins than VT500 cells, a Daudi-derived CD77-deficient mutant cell line. In contrast, MHC class II-mediated adhesion and surface expression are similar in the two cell lines. Therefore, CD77 could play a functional or regulatory role in MHC class II-mediated functions specifically relating to antigen presentation by B-cells to T helper cells.
George
T
T
Department of Biology, Spelman College, Atlanta, Georgia 30314-4399, USA.
Boyd
B
B
Price
M
M
Lingwood
C
C
Maloney
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D002448:Cell Adhesion; D015798:HLA-DR1 Antigen / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D022622:Shiga Toxin 1 / Q000737:chemistry / Q000378:metabolism*; D022641:Shiga Toxin 2 / Q000737:chemistry / Q000378:metabolism; D014281:Trihexosylceramides / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D021122:Protein Subunits; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D014281:Trihexosylceramides; C018549:globotriaosylceramide