DRB1*1316: evolutionary and functional implications of a novel polymorphism at codon 86

Area of Science:

• Immunogenetics
• Molecular biology
• Human leukocyte antigen (HLA) system

Background:

• Human Leukocyte Antigen (HLA)-DRB1 molecules exhibit significant polymorphism within the antigen-binding site (ABS).
• Position 86 of HLA-DRB1 influences a hydrophobic pocket crucial for peptide anchoring.
• Existing data show exclusive observation of Valine or Glycine at position 86 in thousands of specimens.

Purpose of the Study:

• To report the nucleotide sequence of a novel HLA-DRB1 allele, HLA-DRB1*1316.
• To characterize the polymorphism at position 86 in this new allele.
• To assess the significance of this rare polymorphism in HLA-DRB1 evolution and structure-function hypotheses.

Main Methods:

• Nucleotide sequencing of the HLA-DRB1*1316 allele.
• Comparison of the novel sequence with known HLA-DRB1 alleles (specifically *1301 and *1302).
• Analysis of amino acid changes at codon 86.

Main Results:

• The novel allele HLA-DRB1*1316 shares identity with HLA-DRB1*1301 and *1302 except at codon 86.
• HLA-DRB1*1316 encodes aspartate at position 86.
• This aspartate substitution represents a rare polymorphism, contrasting with the exclusively observed valine or glycine at this position.

Conclusions:

• The discovery of HLA-DRB1*1316 with an aspartate at position 86 introduces a rare polymorphism.
• This finding has implications for evolutionary studies of the HLA system.
• The rare polymorphism provides new insights into the structure-function relationships of HLA-DRB1 molecules.