hla-e: presentation of a broader peptide repertoire impacts the cellular immune response—implications on hsct outcome
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2015
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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.
| Reference Key |
kraemer2015stemhla-e:
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|---|---|
| Authors | ;Thomas Kraemer;Alexander A. Celik;Trevor Huyton;Heike Kunze-Schumacher;Rainer Blasczyk;Christina Bade-Döding |
| Journal | journal of experimental psychology: general |
| Year | 2015 |
| DOI |
10.1155/2015/346714
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| URL | |
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