A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b.

Area of Science:

• Immunology
• Structural Biology
• Molecular Biology

Background:

• The MHC class Ib molecule Qa-1(b) presents leader peptides to CD94-NKG2 receptors on NK and T cells.
• While the function of its ortholog HLA-E is understood, the molecular basis of Qa-1(b) function remains unclear.

Purpose of the Study:

• To elucidate the molecular basis of Qa-1(b) function by assessing its interaction with CD94-NKG2A.
• To determine the structure of Qa-1(b) bound to a leader sequence peptide and compare it with HLA-E.

Main Methods:

• Surface plasmon resonance to assess Qa-1(b)-CD94-NKG2A interaction affinity.
• X-ray crystallography to determine the 1.9 Å resolution structure of Qa-1(b) bound to the Qdm peptide (AMAPRTLLL).
• Comparative structural analysis of Qa-1(b) and HLA-E.

Main Results:

• Qa-1(b) and CD94-NKG2A interact with an affinity of 17 μM.
• The crystal structure of Qa-1(b)-Qdm complex revealed similarities to HLA-E but significant differences in the Ag-binding cleft.
• Despite conserved peptide conformation, structural differences between Qa-1(b) and HLA-E lead to species-specific CD94-NKG2A ligand recognition.

Conclusions:

• Structural homology exists between Qa-1(b) and HLA-E.
• Differences in Ag-binding clefts explain Qa-1(b)'s restricted peptide repertoire.
• Structural insights provide a basis for understanding Qa-1(b) specificity in CD94-NKG2 receptor interactions.