MHC class II-peptide complexes and APC lipid rafts accumulate at the immunological synapse.
Activation of CD4(+) Th cells requires their cognate interaction with APCs bearing specific relevant MHC class II-peptide complexes. This cognate interaction culminates in the formation of an immunological synapse that contains the various proteins and lipids required for efficient T cell activation. We now show that APC lipid raft membrane microdomains contain specific class II-peptide complexes and serve as platforms that deliver these raft-associated class II molecules to the immunological synapse. APC rafts are required for T cell:APC conjugate formation and T cell activation at low densities of relevant class II-peptide complexes, a requirement that can be overcome at high class II-peptide density. Analysis of confocal microscopy images revealed that over time APC lipid rafts, raft-associated relevant class II-peptide complexes, and even immunologically irrelevant class II molecules accumulate at the immunological synapse. As the immunological synapse matures, relevant class II-peptide complexes are sorted to a central region of the interface, while irrelevant class II molecules are excluded from this site. We propose that T cell activation is facilitated by recruitment of MHC class II-peptide complexes to the immunological synapse by virtue of their constitutive association with lipid raft microdomains.
Hiltbold
Elizabeth M
EM
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Poloso
Neil J
NJ
Roche
Paul A
PA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D010446:Peptide Fragments; C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase