Decreased specific CD8+ T cell cross‐reactivity of antigen recognition following vaccination with Melan‐A peptide

Abstract

The aim of T cell vaccines is the expansion of antigen‐specific T cells able to confer immune protection against pathogens or tumors. Although increase in absolute cell numbers, effector functions and TCR repertoire of vaccine‐induced T cells are often evaluated, their reactivity for the cognate antigen versus their cross‐reactive potential is rarely considered. In fact, little information is available regarding the influence of vaccines on T cell fine specificity of antigen recognition despite the impact that this feature may have in protective immunity. To shed light on the cross‐reactive potential of vaccine‐induced cells, we analyzed the reactivity of CD8⁺ T cells following vaccination of HLA‐A2⁺ melanoma patients with Melan‐A peptide, incomplete Freund's adjuvant and CpG‐oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan‐A‐reactive CD8⁺ T cells in vivo. A collection of predicted Melan‐A cross‐reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan‐A‐reactive CD8⁺ T cell clones. While Melan‐A‐reactive CD8⁺ T cells prior to vaccination are usually constituted of widely cross‐reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest. Importantly, these cells are tumor‐reactive.