Location of major histocompatibility complex class II molecules in rafts on dendritic cells enhances the efficiency of T-cell activation and proliferation.
The existence of major histocompatibility complex (MHC) class II molecules in lipid rafts has been described in dendritic cells (DC); however, the importance of rafts in T-cell activation has not been clarified. In this study, the distribution of the lipid raft components (CD59 and GM1 ganglioside) in human monocyte-derived DC was investigated. DC had an even distribution of these components at the cell surface. In addition, raft-associated GM1 ganglioside colocalized with cross-linked MHC class II. This implies coaggregation of raft components with these MHC molecules, which may be important in the interaction between T cells and antigen-presenting cells. In studies carried out to investigate the effect of the DC : T-cell interaction on raft distribution, we found a clustering of the lipid raft component CD59 on DC at the synaptic interface, with associated activation of the interacting T cell. In an antigen-specific response between DC and CD4+ T-cell clones, disruption of lipid rafts resulted in inhibition of both CD59 clustering and T-cell activation. This was most pronounced when limiting amounts of cognate peptide were used. Together, these data demonstrate the association of MHC class II with lipid rafts during DC : T-cell interaction and suggest an important role for DC lipid rafts in T-cell activation.
Eren
E
E
Department of Immunology, Imperial College London, Hammersmith Campus, London, UK.
Yates
J
J
Cwynarski
K
K
Preston
S
S
Dong
R
R
Germain
C
C
Lechler
R
R
Huby
R
R
Ritter
M
M
Lombardi
G
G
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018957:CD59 Antigens / Q000032:analysis*; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005677:G(M1) Ganglioside / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology*
D018957:CD59 Antigens; D000949:Histocompatibility Antigens Class II; D005677:G(M1) Ganglioside