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

Eur J Immunol. 2010 Jan;40(1):91-102. doi: 10.1002/eji.200939225.

Abstract

In humans, several HLA-DRB loci (DRB1/3/4/5) encode diverse beta-chains that pair with alpha-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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation*
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • HLA-DR Antigens / chemistry
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • HLA-DRB3 Chains
  • Humans
  • Molecular Sequence Data
  • Monocytes / immunology
  • RNA, Messenger / genetics
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB3 Chains
  • RNA, Messenger