title: HLA-E: Presentation of a Broader Peptide Repertoire Impacts the Cellular Immune Response-Implications on HSCT Outcome.
abstract: The HLA-E locus encodes a nonclassical class Ib molecule that serves many immune functions from inhibiting NK cells to activating CTLs. Structural analysis of HLA-E/NKG2A complexes visualized fine-tuning of protective immune responses through AA interactions between HLA-E, the bound peptide, and NKG2A/CD94. A loss of cellular protection through abrogation of the HLA-E/NKG2A engagement is dependent on the HLA-E bound peptide. The role of HLA-E in posttransplant outcomes is not well understood but might be attributed to its peptide repertoire. To investigate the self-peptide repertoire of HLA-E (∗) 01:01 in the absence of protective HLA class I signal peptides, we utilized soluble HLA technology in class I negative LCL cells in order to characterize HLA-E (∗) 01:01-bound ligands by mass-spectrometry. To understand the immunological impact of these analyzed ligands on NK cell reactivity, we performed cellular assays. Synthesized peptides were loaded onto recombinant T2 cells expressing HLA-E (∗) 01:01 molecules and applied in cytotoxicity assays using the leukemia derived NK cell line (NKL) as effector. HLA-E in complex with the self-peptides demonstrated a shift towards cytotoxicity and a loss of cell protection. Our data highlights the fact that the HLA-E-peptidome is not as restricted as previously thought and support the suggestion of a posttransplant role for HLA-E.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraemer
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Celik
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Trevor
authors.initials: T
authors.lastname: Huyton
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Kunze-Schumacher
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bade-Döding