HLA-E: Presentation of a Broader Peptide Repertoire Impacts the Cellular Immune Response—Implications on HSCT Outcome

Abstract EN

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.