Dendritic cell (DC) subsets with biased capacity for CD4⁺ and CD8⁺ T cell activation are asymmetrically distributed in lymph nodes (LNs), but how this affects adaptive responses has not been extensively studied. Here we used quantitative imaging to examine the relationships among antigen dispersal, DC positioning, and T cell activation after protein immunization. Antigens rapidly drained into LNs and formed gradients extending from the lymphatic sinuses, with reduced abundance in the deep LN paracortex. Differential localization of DCs specialized for major histocompatibility complex I (MHC I) and MHC II presentation resulted in preferential activation of CD8⁺ and CD4⁺ T cells within distinct LN regions. Because MHC I–specialized DCs are positioned in regions with limited antigen delivery, modest reductions in antigen dose led to a substantially greater decline in CD8⁺ compared with CD4⁺ T cell activation, expansion, and clonal diversity. Thus, the collective action of antigen dispersal and DC positioning regulates the extent and quality of T cell immunity, with important implications for vaccine design.

具有CD4 ⁺和CD8 ⁺ T细胞活化能力的树突状细胞（DC）子集不对称地分布在淋巴结（LNs）中，但是尚未广泛研究其如何影响适应性反应。在这里，我们使用定量成像来检查蛋白质免疫后抗原扩散，DC定位和T细胞活化之间的关系。抗原迅速排入LNs，并形成从淋巴窦延伸的梯度，降低了深层LN旁皮质的丰度。专用于主要组织相容性复合体I（MHC I）和MHC II呈递的DC的差异化定位导致CD8 ⁺和CD4 ^+的优先激活不同LN区域内的T细胞。由于MHC I特异的DC位于抗原传递受限的区域，与CD4 ⁺ T细胞的活化，扩增和克隆多样性相比，抗原剂量的适度降低导致CD8 ^+的下降幅度更大。因此，抗原分散和DC定位的共同作用调节了T细胞免疫的程度和质量，对疫苗设计具有重要意义。