Reassessing the role of HLA-DRB3 T-cell responses: evidence for significant expression and complementary antigen presentation.
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.
Faner
Rosa
R
Laboratory of Immunobiology Research and Applications to Diagnosis (LIRAD). Banc de Sang i Teixits, Badalona, Spain.
James
Eddie
E
Huston
Laurie
L
Pujol-Borrel
Ricardo
R
Kwok
William W
WW
Juan
Manel
M
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D012333:RNA, Messenger