The replacement mutation in HLA-DRB1*1211 affects a likely keystone position.
Currently, 10 different amino acid variants of the HLA-DRB1*12 family are known. We here report the identification of a new HLA-DRB1*12 allele in a healthy Caucasian male individual. The allele was detected by sequencing-based typing during confirmatory high-resolution typing of an unrelated, male, potential donor from the Czech National Marrow Donors Registry. Compared with DRB1*120101, to which it is closest, the new variant is characterized by a new replacement mutation (T-->C) at nucleotide position 126 of exon 2, resulting in the amino acid substitution Phe-->Leu at position 47. Computational analysis reveals that position 47 functions as a keystone in the beta(1) domain, joining both segments of the alpha helix with the beta sheet, and plays a major role in the structural conformation of the binding groove. Additionally, position 47 is part of pocket E of the peptide binding groove and is directly involved in peptide binding. The new allele, DRB1*1211, is therefore likely to differ substantially from other DRB1*12 alleles in its peptide binding repertoire and alloreactive potential.
Horn
Peter A
PA
Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
DeLuca
David S
DS
Jindra
Pavel
P
Blasczyk
Rainer
R
D019943:Amino Acid Substitution; D018360:Crystallography, X-Ray; D018153:Czech Republic; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011487:Protein Conformation; D044465:White People
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains