Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity

J Immunol. 2009 Aug 15;183(4):2425-34. doi: 10.4049/jimmunol.0900581. Epub 2009 Jul 20.

Abstract

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8(+) cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8(+) T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2D(d) better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8(+) T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics*
  • AIDS Vaccines / immunology*
  • AIDS Vaccines / metabolism
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Line
  • Cells, Cultured
  • Clone Cells
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / metabolism
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / immunology
  • Genetic Vectors / metabolism
  • H-2 Antigens / administration & dosage
  • H-2 Antigens / genetics*
  • H-2 Antigens / immunology*
  • H-2 Antigens / metabolism
  • HIV Envelope Protein gp120 / administration & dosage
  • HIV Envelope Protein gp120 / genetics*
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • Histocompatibility Antigen H-2D
  • Immunization, Secondary
  • Mice
  • Mice, Inbred BALB C
  • Protein Binding / genetics
  • Protein Binding / immunology

Substances

  • AIDS Vaccines
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • HIV Envelope Protein gp120
  • Histocompatibility Antigen H-2D