TY - JOUR
T1 - Reassessing the role of HLA-DRB3 T-cell responses: Evidence for significant expression and complementary antigen presentation
AU - Faner, Rosa
AU - James, Eddie
AU - Huston, Laurie
AU - Pujol-Borrel, Ricardo
AU - Kwok, William W.
AU - Juan, Manel
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Antigen presentation
KW - APC
KW - Cd4 t cells +
KW - Mhc class ii
KW - Molecular immunology
U2 - 10.1002/eji.200939225
DO - 10.1002/eji.200939225
M3 - Article
VL - 40
SP - 91
EP - 102
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -