Full-length HLA-DPB1 diversity in multiple alleles of individuals from Caucasian, Black, or Oriental origin.
Despite DP antigens have been shown to be stimulators of the mixed lymphocyte reaction, human leukocyte antigen-DPB1 is not considered in the matching criteria for hematopoietic stem cell transplantation (HSCT). The role of DPB1 matching in HSCT remains inconclusive because of contradictory findings in different studies. The concept of permissible and non-permissible mismatches might clarify these contradictory results. Although several groups have attempted to identify immunogenic epitopes in exon 2 to establish permissive and non-permissive allele groups, the direct correlation between individual exon 2 amino acids and epitopes with DPB1 immunogenicity is still not evident. We hypothesize that polymorphism within the entire molecule, including polymorphic variability in different ethnic groups, is crucial to unravel the function of DPB1 polymorphism. Using an RNA-based approach, we sequenced all frequent and available non-frequent DPB1 alleles full length from 148 samples representing 28 different DPB1 alleles from either Black, Caucasian, or Oriental origin. We identified various DPB1 alleles with, in addition to the exon 2 polymorphism, polymorphisms in exons 1, 3, 4, and 5. Based on this polymorphism outside exon 2, we defined one new allele. Two alleles with identical exon 2 polymorphism but differing outside exon 2 were identified in individuals of different ethnic groups. As T cell binding is not restricted to the polymorphic groove and polymorphism in the β2 domain of the DP molecule affects CD4 interaction, full-length polymorphism should be considered to determine immunogenicity. Eventually, this knowledge will provide new insights in the classification of DPB1 polymorphism and more importantly will add new perspectives to the concept of permissiveness in transplantation.
Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Centre, The Netherlands.
N
N
Lauterbach
C E M
CE
Voorter
C M H A
CM
Stallinga
M
M
Groeneweg
L
L
Wieten
M G J
MG
Tilanus
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D014644:Genetic Variation; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D044465:White People / Q000235:genetics*
D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen