Evaluating the potential impact of mismatches outside the antigen recognition site in unrelated hematopoietic stem cell transplantation: HLA-DRB1*1454 and DRB1*140101.
DNA sequencing of 268 individuals drawn from four US populations carrying two unresolved DRB1*14 alleles differing only outside the antigen recognition site identified DRB1*1454 in the majority. A database of 4222 human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation donor-recipient pairs was queried to determine the number likely mismatched for DRB1*140101/DRB1*1454 but matched for class I loci. A power calculation suggests that more than 88,000 transplants among European Americans will be needed to identify sufficient 7/8 allele-matched pairs to evaluate the impact of the DRB1*140101/DRB1*1454 mismatch on transplant outcome. Molecular modeling of the HLA-DR interaction with the T-cell receptor and with CD4 suggests that the amino acid substitution distinguishing the two alleles will have minimal impact on allorecognition.
Xiao
Y
Y
Department of Pediatrics and Oncology, C.W. Bill Young Marrow Donor Research and Recruitment Program, Georgetown University Medical Center, Washington, DC 20057, USA.
Lazaro
A M
AM
Masaberg
C
C
Haagenson
M
M
Vierra-Green
C
C
Spellman
S
S
Dakshanamurthy
S
S
Ng
J
J
Hurley
C K
CK
D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D020137:Base Pair Mismatch; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004252:DNA Mutational Analysis; D005787:Gene Frequency / Q000235:genetics*; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics*; D059811:HLA-DRB1 Chains; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
D015704:CD4 Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C541271:HLA-DRB1*14:01 antigen; C541272:HLA-DRB1*14:54 antigen