Human T cell receptor-mediated recognition of HLA-E

Area of Science:

• Immunology
• Molecular Biology
• Cellular Biology

Background:

• Human Leukocyte Antigen-E (HLA-E) is a non-classical MHC class Ib molecule.
• HLA-E presents hydrophobic peptides derived from leader sequences of other HLA class I molecules.
• These peptides serve as ligands for CD94/NKG2 lectin-like receptors on NK cells and some T cells.

Purpose of the Study:

• To characterize the recognition specificity of a human CD94+ T cell clone (K14).
• To investigate the role of the alpha beta T cell receptor (TCR) in HLA-E mediated recognition.
• To determine if HLA-E can present viral peptides for T cell recognition.

Main Methods:

• Cytolytic assays using RMA-S/HLA-E transfected cells loaded with synthetic peptides.
• Analysis of T cell clone K14 recognition patterns compared to CD94/NKG2C+ NK clones.
• Inhibition assays using anti-CD94 and anti-clonotypic T cell receptor (TCR) monoclonal antibodies (mAbs).
• HLA-E tetramer staining with various peptides.

Main Results:

• The CTL clone K14 displayed a distinct recognition pattern of HLA-E loaded peptides compared to NK clones.
• K14 recognized HLA-E loaded with certain HLA class I leader sequence peptides and an Epstein-Barr virus peptide.
• Cytotoxicity of K14 against RMA-S/HLA-E was inhibited by anti-clonotypic mAb, not anti-CD94 mAb.
• HLA-E tetramer binding to K14 cells was dependent on the TCR and minimally affected by anti-CD94.

Conclusions:

• Human alpha beta T cells can recognize HLA-E molecules presenting class I-derived and viral peptides.
• This recognition is mediated through the alpha beta TCR, independent of the CD94/NKG2 pathway.
• The findings suggest a novel pathway for T cell surveillance involving HLA-E.