Characterization of four new HLA alleles: HLA-B*15:01:18, HLA-B*44:110, HLA-C*04:01:22
and HLA-DQB 1*05:14
J. Heyder
∗
, A. Heinold, G. Fiedler, G. Opelz & T. H. Tran
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany
* Present address: Institute of Legal Medicine, University of Munich, Munich, Germany
Key words: HLA-B*15:01:18 ; HLA-B*44:110 ; HLA-C*04:01:22; HLA-DQB1*05:14; PCR-SBT
We describe four novel HLA alleles, HLA-B*15:01:18,
HLA-B*44:110, HLA-C*04:01:22 and HLA-DQB1*05:14.
Four novel human leukocyte antigens (HLA)-B*15:01:18
(EMBL; FN689350), -B*44:110 (EMBL; FN689351), -
C*04:01:22 (EMBL; FN995095) and -DQB1*05:14 (Gen-
bank, HE584761) were identified by polymerase chain reac-
tion sequence-based typing (PCR-SBT) of three unrelated
hematopoietic stem cell donors and a deceased kidney donor.
All donors were of Caucasoid origin.
HLA-B*15:01:18 differs from HLA-B*15:01:01:01 by a
single nucleotide exchange (G > A) at position 902 (codon
152) in exon 3 (Figure 1A). This does not result in a change
of the amino acid coding (glutamic acid). Analyzing the
sequences of all known HLA class I alleles showed that only
B*49:01:02 showed the sequence motif ‘GAA’ at codon 152
as seen in the new allele B*15:01:18. Because B*49:01:02
has a low allele frequency, we hypothesize that the novel allele
B*15:01:18 has emerged from a point mutation rather than
from a crossover between B*15:01:01:01 and B*49:01:02.
The complete typing of the female stem cell donor was
A*02:01, *03:01 ; B*07:02, *15:01:18 ; C*03:04, *07:02 ;
DRB1*07, *11 and DQB1*02:02, *03:01. Based on linkage
disequilibrium information for the most closely related allele
B*15:01:01:01, the B*15:01:18 -bearing haplotype could be
A*02:01 – B*15:01 – C*03:04 (1).
Compared with HLA-B*44:03:01, HLA-B*44:110 has a
non-synonymous nucleotide exchange (G > C) at position
735 in exon 3 (Figure 1B). This alters the amino acid
coding from arginine to serine at codon 97. Residue 97
is part of the peptide-binding pocket of HLA-B molecules
(2). An amino acid exchange of arginine with a charged
polar residue to serine with an uncharged polar character
© 2011 John Wiley & Sons A/S 209
Tissue Antigens, 2012, 79, 204–217