HLP-DR/DQ transgenic, class II deficient mice as a novel model to select for HSP T cell epitopes with immunotherapeutic or preventative vaccine potential

A. Geluk, Veena D Taneja, K. E. Van Meijgaarden, R. R P De Vries, C. S. David, T. H M Ottenhoff

Research output: Contribution to journalArticle

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Abstract

Protective immunity against mycobacteria is dependent on antigen/MHC class II specific, CD4+ Th 1 cells. HLA-DR3-restricted Th1 cells respond to a subset of mycobacterial antigens, including the immunodominant hsp65, and recognize a single epitope in hsp65, notably p1-20. Altered peptide ligands (APL) of p1-20 can inhibit p1-20/hsp65 induced proliferation of DR3- restricted T cells in an allele specific manner in vitro. In order to develop a preclinical model in which p1-20 APL can be tested in vivo in the context of HLA, we have used murine class II deficient, HLA transgenic (Ab0) mice, in which all CD4+ T cells are restricted by the tg HLA molecule. BCG- immunized DR3.Ab0 and DQ8.Ab0 mice both responded well to hsp65. Furthermore, DR3.Ab0 mice recognized precisely the same p1-20 epitope as DR3-restricted human T cells, whereas DQ8.Ab0 mice responded to a different set of hsp65 peptides. This shows that (i) the same immunodominant protein and peptide epitope are recognized by T cells from DR3.Ab0 mice and DR3+ humans and (ii) indicates the major role of HLA-polymorphism in controlling the human T cell response to mycobacterial antigens. Thus, HLA-transgenic, Ab0 mice provide a novel, preclinical model system to analyze APL and vaccines in the context of HLA polymorphism.

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalBiotherapy
Volume10
Issue number3
StatePublished - 1998

Fingerprint

T-Lymphocyte Epitopes
Vaccines
T-Lymphocytes
Peptides
Ligands
Transgenic Mice
Epitopes
HLA-DR3 Antigen
Immunodominant Epitopes
Th1 Cells
Subunit Vaccines
Histocompatibility Antigens Class II
Mycobacterium
Mycobacterium bovis
Immunity
Alleles
Antigens
Proteins

Keywords

  • HLA-DR
  • hsp65
  • Immunoregulation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Geluk, A., Taneja, V. D., Van Meijgaarden, K. E., De Vries, R. R. P., David, C. S., & Ottenhoff, T. H. M. (1998). HLP-DR/DQ transgenic, class II deficient mice as a novel model to select for HSP T cell epitopes with immunotherapeutic or preventative vaccine potential. Biotherapy, 10(3), 191-196.

HLP-DR/DQ transgenic, class II deficient mice as a novel model to select for HSP T cell epitopes with immunotherapeutic or preventative vaccine potential. / Geluk, A.; Taneja, Veena D; Van Meijgaarden, K. E.; De Vries, R. R P; David, C. S.; Ottenhoff, T. H M.

In: Biotherapy, Vol. 10, No. 3, 1998, p. 191-196.

Research output: Contribution to journalArticle

Geluk, A. ; Taneja, Veena D ; Van Meijgaarden, K. E. ; De Vries, R. R P ; David, C. S. ; Ottenhoff, T. H M. / HLP-DR/DQ transgenic, class II deficient mice as a novel model to select for HSP T cell epitopes with immunotherapeutic or preventative vaccine potential. In: Biotherapy. 1998 ; Vol. 10, No. 3. pp. 191-196.
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