TY - JOUR
T1 - Targeting antigen to CD19 on B cells efficiently activates T cells
AU - Yan, Jun
AU - Wolff, Martin J.
AU - Unternaehrer, Julia
AU - Mellman, Ira
AU - Mamula, Mark J.
N1 - Funding Information:
This study was supported by grants from the SLE Foundation to J.Y., the Ethel F. Donaghue Women’s Investigator Program at Yale University and the National Institutes of Health (NIH) (AR41032, AI-36529 and AI-48120) to M.J.M. The work was also supported by NIH grant AI-34098 and the Ludwig Institute for Cancer Research to I.M. We would like to thank Renelle Gee for her outstanding technical assistance and Mark Shlomchik for his important scientific discussion and reviewing the manuscript.
PY - 2005/7
Y1 - 2005/7
N2 - CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells. © The Japanese Society for Immunology 2005. All rights reserved.
AB - CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells. © The Japanese Society for Immunology 2005. All rights reserved.
KW - Antigen presentation
KW - CD19
KW - T cell activation
UR - http://www.scopus.com/inward/record.url?scp=26444605553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26444605553&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/82ba7857-c633-3a8f-9497-78e7a9f19a6c/
U2 - 10.1093/intimm/dxh266
DO - 10.1093/intimm/dxh266
M3 - Article
C2 - 15967786
SN - 0953-8178
VL - 17
SP - 869
EP - 877
JO - International Immunology
JF - International Immunology
IS - 7
ER -