tetraspanin CD9 mediates lateral association of MHC class II molecules on the dendritic cell surface

We have found that MHC class II (MHC II) molecules exhibit a distinctive organization on the dendritic cell (DC) plasma membrane. Both in DC lysates and on the surface of living cells, I-A and I-E molecules engaged in lateral interactions not observed on other antigen-presenting cells such as B blas...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 104; no. 1; pp. 234 - 239
Main Authors Unternaehrer, Julia J, Chow, Amy, Pypaert, Marc, Inaba, Kayo, Mellman, Ira
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 02.01.2007
National Acad Sciences
Subjects
Animals
Antigen Presentation
Antigens
Antigens, CD - chemistry
Antigens, CD - physiology
B lymphocytes
B-Lymphocytes - immunology
B7-1 Antigen - analysis
B7-2 Antigen - analysis
Biological Sciences
Blasts
Cell lines
Cellular biology
Dendritic Cells - immunology
Fluorescence
Histocompatibility Antigens Class II - analysis
Histocompatibility Antigens Class II - chemistry
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - physiology
Mice
Mice, Inbred C57BL
Molecular interactions
Molecules
Surface areas
T cell antigen receptors
T cell receptors
T lymphocytes
Tetraspanin-29
Western blotting
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Summary:We have found that MHC class II (MHC II) molecules exhibit a distinctive organization on the dendritic cell (DC) plasma membrane. Both in DC lysates and on the surface of living cells, I-A and I-E molecules engaged in lateral interactions not observed on other antigen-presenting cells such as B blasts. Because DCs and B blasts express MHC II at comparable surface densities, the interaction was not due to simple mass action. Instead, it reflected the selective expression of the tetraspanin CD9 at the DC surface. I-A and I-E molecules coprecipitated with each other and with CD9. The association of heterologous MHC II molecules was abrogated in DCs from CD9⁻/⁻ mice. Conversely, expression of exogenous CD9 in B cells induced MHC II interactions. CD9 is thus necessary for the association of heterologous MHC II, a specialization that would facilitate the formation of MHC II multimers expected to enhance T cell receptor stimulation by DCs.
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Communicated by Mark M. Davis, Stanford University School of Medicine, Stanford, CA, November 1, 2006
Present address: Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115.
Author contributions: J.J.U., K.I., and I.M. designed research; J.J.U. and M.P. performed research; J.J.U. and A.C. contributed new reagents/analytic tools; J.J.U., M.P., K.I., and I.M. analyzed data; and J.J.U. and I.M. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0609665104