Receptor-Facilitated Antigen Presentation Requires the Recruitment of B Cell Linker Protein to Igα

• Published in: The Journal of immunology (1950) 2002-03, Vol.168 (5), p.2127-2138
• Main Authors: Siemasko, Karyn, Skaggs, Brian J., Kabak, Shara, Williamson, Edward, Brown, Bruce K., Song, Wenxia, Clark, Marcus R.
• Format: Article
• Language: English
• Subjects: immunoreceptor tyrosine-based activation motif
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.5.2127

Ags that cross-link the B cell Ag receptor are preferentially and rapidly delivered to the MHC class II-enriched compartment for processing into peptides and subsequent loading onto MHC class II. Proper sorting of Ag/receptor complexes requires the recruitment of Syk to the phosphorylated immunoreceptor tyrosine-based activation motif tyrosines of the B cell Ag receptor constituent Igα. We postulated that the Igα nonimmunoreceptor tyrosine-based activation motif tyrosines, Y176 and Y204, contributed to receptor trafficking. Igα(YΔF176,204)/Igβ receptors were targeted to late endosomes, but were excluded from the vesicle lumen and could not facilitate the presentation of Ag to T cells. Subsequent analysis demonstrated that phosphorylation of Y176/Y204 recruited the B cell linker protein, Vav, and Grb2. Reconstitution of Igα(YΔF176,204)/Igβ with the B cell linker protein rescued both receptor-facilitated Ag presentation and entry into the MHC class II-enriched compartment. Thus, aggregation accelerates receptor trafficking by recruiting two separate signaling modules required for transit through sequential checkpoints.