The replacement mutation in HLA-DRB1*1211 affects a likely keystone position

Area of Science:

• Immunogenetics
• Molecular Biology
• Human Leukocyte Antigen (HLA) system

Background:

• The HLA-DRB1*12 family comprises 10 known amino acid variants.
• HLA alleles are crucial for immune system function and transplantation compatibility.

Purpose of the Study:

• To report the identification and characterization of a novel HLA-DRB1*12 allele.
• To investigate the potential functional impact of this new allele on peptide binding and immune recognition.

Main Methods:

• Sequencing-based typing for high-resolution HLA typing.
• Identification of nucleotide and amino acid substitutions.
• Computational analysis of the structural and functional significance of the mutation.

Main Results:

• A new HLA-DRB1*12 allele, designated DRB1*1211, was identified in a healthy Caucasian male.
• The new allele differs from DRB1*120101 by a T-to-C mutation at nucleotide position 126 in exon 2, causing a Phe-to-Leu substitution at amino acid position 47.
• Position 47 is critical for the structural conformation of the peptide binding groove and directly influences peptide binding.

Conclusions:

• The novel HLA-DRB1*1211 allele possesses a unique amino acid substitution at a functionally significant position.
• This alteration is predicted to modify the peptide-binding repertoire and alloreactive potential compared to other DRB1*12 alleles.
• Further studies are warranted to fully elucidate the immunological implications of DRB1*1211.