Article: article from journal or magazin.
Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
European journal of immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
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.
Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cells, Cultured, Cross-Priming, Epitopes, T-Lymphocyte, Humans, Melanoma, Neoplasm Proteins, Peptide Fragments, Vaccines, Subunit
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