Reassessing the role of HLA-DRB3 T-cell responses: Evidence for significant expression and complementary antigen presentation

Rosa Faner, Eddie James, Laurie Huston, Ricardo Pujol-Borrel, William W. Kwok, Manel Juan

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14 Citations (Scopus)

Abstract

In humans, several HLA-DRB loci (DRB1/3/4/5) encode diverse β-chains that pair with α-chains to form DR molecules on the surface of APC. While DRB1 and DRB5 have been extensively studied, the role of DRB3/4 products of DR52/DR53 haplotypes has been largely neglected. To clarify the relative expression of DRB3, we quantified DRB3 mRNA levels in comparison with DRB1 mRNA from the same haplotype in both B cells and monocytes, observing quantitatively significant DRB3 synthesis. In CD19+ cells, DRB1*03/11/13 was 3.5-fold more abundant than DRB3, but in CD14+ this difference was only two-fold. Monocytes also had lower overall levels of DR mRNA compared with B cells, which was confirmed by cell surface staining of DRB1 and DRB3. To evaluate the functional role of DRB3, tetramer-guided epitope mapping was used to detect T cells against tetanus toxin and several influenza antigens presented by DRB3*0101/0202 or DRB1*03/11/13. None of the epitopes discovered were shared among any of the DR molecules. Quantitative assessment of DRB3-tetanus toxin specific T cells revealed that they are present at similar frequencies as those observed for DRB1. These results suggest that DRB3 plays a significant role in antigen presentation with different epitopic preferences to DRB1. Therefore, DRB3, like DRB5, serves to extend and complement the peptide repertoire of DRB1 in antigen presentation. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Original languageEnglish
Pages (from-to)91-102
JournalEuropean Journal of Immunology
Volume40
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Antigen presentation
  • APC
  • Cd4 t cells +
  • Mhc class ii
  • Molecular immunology

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