A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses

Jorgen Schøller; Mahavir Singh; Lesley Bergmeier; Katja Brunstedt; Yufei Wang; Trevor Whittall; Durdana Rahman; J Pido-Lopez; T Lehner

doi:10.1016/j.jim.2010.05.008

A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses

J Immunol Methods. 2010 Aug 31;360(1-2):1-9. doi: 10.1016/j.jim.2010.05.008. Epub 2010 Jun 10.

Authors

Jorgen Schøller¹, Mahavir Singh, Lesley Bergmeier, Katja Brunstedt, Yufei Wang, Trevor Whittall, Durdana Rahman, J Pido-Lopez, T Lehner

Affiliation

¹ Immudex, Copenhagen, Denmark.

PMID: 20542039
DOI: 10.1016/j.jim.2010.05.008

Abstract

The objective of this study was to produce and evaluate the immunogenic potential of a recombinant HLA-class I antigen linked to dextran. The HLA-A*0201 heavy chain and beta2 microglobulin were cloned by PCR amplification of overlapping oligonucleotides and produced in E. coli. These were assembled with a CMV binding peptide motif, the HLA complex was biotinylated and bound by streptavidin coated dextran at a ratio of 24 HLA to 1 dextran molecule (termed Dextramer). Allostimulation of human PBMC in vitro and in vivo immunization of Balb c mice with the HLA-A*0201 construct elicited CD4+ and CD8+ T cell proliferative responses, IgG specific antibodies in mice and in human T cell proliferation and APOBEC3G mRNA. These adaptive and innate immune responses induced by a novel recombinant HLA construct in human cells and mice suggest their application as a potential vaccine candidate against HIV infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines*
Adaptive Immunity / drug effects
Animals
Antibody Formation / drug effects
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism*
CD4-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / pathology
Cell Proliferation / drug effects
Cells, Cultured
Cloning, Molecular
Dextrans / genetics
Dextrans / metabolism
Dextrans / pharmacology*
HLA-A Antigens / genetics
HLA-A Antigens / metabolism*
HLA-A Antigens / pharmacology
HLA-A2 Antigen
Humans
Immunity, Innate / drug effects
Immunization
Immunoglobulin G / blood
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Protein Binding
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology*

Substances

AIDS Vaccines
Dextrans
HLA-A Antigens
HLA-A*02:01 antigen
HLA-A2 Antigen
Immunoglobulin G
Recombinant Proteins