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

Eur J Immunol. 2006 Jul;36(7):1805-14. doi: 10.1002/eji.200535805.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cells, Cultured
  • Cross-Priming / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Humans
  • MART-1 Antigen
  • Melanoma / immunology
  • Melanoma / therapy
  • Neoplasm Proteins / administration & dosage
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Peptide Fragments
  • Vaccines, Subunit