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Effective CD4 T cell priming requires repertoire scanning by CD301b+ migratory cDC2 cells upon lymph node entry

Tatsumi, N;Codrington, AL;El-Fenej, J;Phondge, V;Kumamoto, Y;

During the initiation of adaptive immune responses, millions of lymphocytes must be scanned to find the few cognate clones. The activation mechanisms of CD4 T cells have been extensively studied, but the cellular mechanisms that drive selection of cognate clones are not completely understood. Here, we show that recently homed naïve polyclonal CD4 T cells are temporarily retained before leaving the lymph node. This stop-and-go traffic of CD4 T cells provides an adequate time window for efficient scanning and timely priming of antigen-specific cognate clones. CD301b+ DCs, a major subset of migratory cDC2 cells, localize to the areas around high endothelial venules, where they retain incoming polyclonal CD4 T cells through MHCII-dependent but antigen-independent mechanisms, while concurrently providing cognate stimuli for priming. These results indicate that CD301b+ DCs function as an immunological “display window” for CD4 T cells to efficiently scan their antigen specificity.