Decreased specific CD8+ Tcell cross-reactivity of antigen recognition following vaccination with Melan-A peptide

• Published in: European Journal of Immunology 2006-07, Vol.36 (7), p.1805-1814
• Main Authors: Appay, Victor, Speiser, Daniel E, Rufer, Nathalie, Reynard, Severine, Barbey, Catherine, Cerottini, Jean-Charles, Leyvraz, Serge, Pinilla, Clemencia, Romero, Pedro
• Format: Article
• Language: English
• ISSN: 0014-2980; 1365-2567
• DOI: 10.1002/eji.200535805

The aim of Tcell vaccines is the expansion of antigen-specific Tcells able to confer immune protection against pathogens or tumors. Although increase in absolute cell numbers, effector functions and TCR repertoire of vaccine-induced Tcells 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 Tcell 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+ Tcells 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+ Tcells 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+ Tcell clones. While Melan-A-reactive CD8+ Tcells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory Tcells displaying a reactivity predominantly restricted to the antigen of interest. Importantly, these cells are tumor-reactive.