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

Appay, V, Speiser, DE, Rufer, N et al. (2006). Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide . 36(7), 1805-1814. 10.1002/eji.200535805

cited authors

  • Appay, V; Speiser, DE; Rufer, N; Reynard, S; Barbey, C; Cerottini, JC; Leyvraz, S; Pinilla, C; Romero, P

authors

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. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

publication date

  • July 1, 2006

Digital Object Identifier (DOI)

start page

  • 1805

end page

  • 1814

volume

  • 36

issue

  • 7