TITLE:
Gender-Biased Regulation of Human IL-17-Producing Cells in Vitro by Peptides Corresponding to Distinct HLA-DRB1 Allele-Coded Sequences
AUTHORS:
Luz P. Blanco, Melissa Plegue, Wai-Ping Fung-Leung, Joseph Holoshitz
KEYWORDS:
MHC Class II; PBMC; TH17; Cytokines; Immune Polarization; Review
JOURNAL NAME:
Journal of Immune Based Therapies, Vaccines and Antimicrobials,
Vol.2 No.3,
July
15,
2013
ABSTRACT: Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (HLA-DRB1*04:01- coded sequence SE motif, QKRAA); 65-79*0402 (HLA-DRB1*04:02-coded sequence SE-negative motif, DERAA); 65-79*0403 (HLA-DRB1*04:03-coded sequence SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females; however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A-positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor’s SE status and gender may both influence TH17 immune polarization.