The membrane distribution of MHC-II-peptide complexes and its role in T cell activation (78.18)

Abstract

The efficiency of the interaction between MHC-II-peptide complexes (pMHC-II) and T cell receptor depends on the amount of antigen present at the surface of DCs. MHC-II molecules are constitutively present in plasma membrane lipid rafts, membrane microdomains that are important to induce T cell activation at low antigen doses. In this work we investigated if DCs can possess a specific pMHC-II distribution at the surface that can enhance T cell activation. In murine bone marrow derived mature DCs (mDCs), MHC-II molecules displayed a clustured phenotype. Using an antibody that recognizes specific IAk-HEL pMHC-II complexes, we observed that pMHC-II also showed a clustered distribution on the surface of antigen-loaded mDCs. While DCs treated with LPS for only 12 h had 50% less IAk-HEL pMHC-II complexes at the cell surface than DCs treated for 30 h, both cell types showed a clustured distribution of these complexes. Despite the fact that 12 h DCs expressed less IAk-HEL pMHC-II complexes and less CD86/CD40 molecules at the cell surface, T cell activation was similar using 12 h- or 30 h-mature DCs. We are currently investigating the relationship between pMHC-II complex number and cluster distribution over time with the antigen presenting cell function to elucidate the role of microdomain association of pMHC-II in T cell activation. This work is supported by NCI.