HLA class I allelic sequence and conformation regulate leukocyte Ig-like receptor binding

Area of Science:

• Immunology
• Molecular Biology

Background:

• Leukocyte Ig-like receptors (LILRs) are key innate immune receptors on myeloid cells.
• LILRs modulate antigen presentation by macrophages and dendritic cells.
• LILR interactions with HLA class I are implicated in disease.

Purpose of the Study:

• To comprehensively assess LILR binding across diverse HLA class I alleles.
• To investigate the influence of HLA class I conformation on LILR recognition.
• To identify novel LILR ligands and understand their disease relevance.

Main Methods:

• Binding assays were performed using over 90 HLA class I alleles.
• Analysis included assessment of LILR interactions with folded and free HLA class I forms.
• Specific amino acid motifs influencing LILR binding were identified.

Main Results:

• LILRB1 and LILRB2 showed allele-specific binding patterns to HLA class I.
• LILRB2 exhibited minimal binding to HLA-B*2705, an allele linked to autoimmune diseases.
• LILRA1 and LILRA3 preferentially bound to HLA-C free heavy chains.

Conclusions:

• HLA allelic variation significantly impacts LILR binding affinity.
• Receptor conformation (folded vs. free heavy chain) dictates LILR binding specificity.
• LILR-mediated recognition of folded vs. unfolded MHC influences immune responses in disease.