Peptide:MHC II complexes derived from a fluorescent antigen were detected in vivo to identify the cells that present subcutaneously injected antigen to CD4 T cells. Skin-derived dendritic cells (DCs) that acquired the antigen while in the draining lymph nodes were the first cells to display peptide:MHC II complexes. Presentation by these cells induced CD69, IL-2 production, and maximal proliferation by the T cells. Later, DCs displaying peptide:MHC II complexes migrated from the injection site via a G protein-dependent mechanism. Presentation by these migrants sustained expression of the IL-2 receptor and promoted delayed type hypersensitivity. Therefore, presentation of peptide:MHC II complexes derived from a subcutaneous antigen occurs in two temporally distinct waves with different functional consequences.
Bibliographical noteFunding Information:
We thank Jennifer Walter for technical assistance; and Kristin Hogquist, Stephen Jameson, Ronald Germain, Alexander Khoruts, Daniel Mueller, and members of the Jenkins group for critical reading of the manuscript and helpful discussions. This work was supported by grants from the NIH (M.K.J.) and the Irvington Institute of Immunological Research (A.A.I.).