کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3257130 | 1207393 | 2012 | 8 صفحه PDF | دانلود رایگان |

Therapies capable of generating host T regulatory cells (TR) responsive to donor-specific HLA-class II minor histocompatibility antigens have the potential to promote tolerance of a transplanted organ. Our group has developed a novel approach for the identification of potentially therapeutic TR target antigens. We perform parallel non-synonymous SNP genotyping of HLA-identical subject pairs to identify peptide variations expressed by only one of the two subjects. Variant peptide pairs are then evaluated for binding a shared HLA-class II allele. Minor peptides predicted to bind HLA-class II with greater affinity than the common variant peptide are tested for HLA class II binding and in vitro induction of suppressive CD4+ T cells. Using this approach we have identified multiple pairs of variant peptides capable of differential binding and induction of suppressive CD4+ T cells. These data demonstrate the feasibility of identifying potentially therapeutic HLA class II minor antigens for generation of donor-specific TR.
► Exome sequencing ~ 4000 to 6000 protein level disparities in unrelated transplants.
► Epitope prediction and peptide binding studies identified 3 novel minor epitopes.
► Two novel minor epitopes were capable of inducing suppressive CD4+ T cells in-vitro.
► Generation of donor specific T regulatory cells is feasible.
Journal: Clinical Immunology - Volume 145, Issue 2, November 2012, Pages 153–160