Checkpoint blockade has cemented the relevance of T cells in the treatment of human cancer. Many types of tumours possess mutations (neo-epitopes) that render them susceptible to destruction by T cells. While checkpoint blockade amplifies pre-existing responses, tumour antigens expressed at low levels may be ineffectively presented for priming T cells and remain immunologically invisible. Vaccines provide a means to elicit robust T cells responses that can further be amplified by blockade immunotherapy. Dendritic cells (DCs) are uniquely equipped to activate T cells and can be harnessed to enhance immunity. An effective method of delivering antigen to DC exploits the fact that DC have unique cell surface receptors, and antibodies against these receptors can be used as vehicles to deliver antigenic cargo. A lead candidate, DEC205, is being assessed in 8 clinical trials for the delivery of cancer vaccines. It was previously assumed that many DC receptors could promote antigen presentation. However, our data reveals that presentation of “peptides“ as opposed to “proteins”, is relatively poorly facilitated by DEC205. We show that Clec9A, another DC-specific molecule, is particularly effective at facilitating the presentation of peptide cargo, leading us to assess its capacity to present peptides encoding neo-tumour epitopes. We provide evidence that Clec9A-targeted neo-antigens can elicit T cell immunity, but not all neo-antigens are equivalent in their capacity to evoke responses. Intriguingly, many of the published neo-antigens are not recognized during tumour rejection, despite this rejection being mediated by T cells. This raises the important question of which neo-antigens drive tumour rejection and how to discriminate effective vaccine candidates from poorly immunogenic neo-antigens. Using several tumour models, published neo-antigens and a suit of newly discovered neo-antigens identified by immunopeptidome analysis, we analyse T cell immunity and its capacity to protect against cancer.