Abstract
Alloreactivity to HLA-DP molecules, class II heterodimers of an oligomorphic alpha and a polymorphic beta chain, is increasingly being studied due to its relevance in clinical transplantation. We hypothesized that not only polymorphisms in the peptide binding groove encoded by exon 2 of HLA-DPB1, but also in other regions of the molecule and the alpha chain, could play a role in CD4+ T cell allorecognition. To test this possibility, we comparatively investigated CD4+ T cell allorecognition, measured by upregulation of the activation marker CD137, against HLA-DPB1*13:01, *05:01, *03:01, *17:01 or their allele counter parts DPB1*107:01, *135:01, *104:01, *131:01, with identical exon 2 sequences but polymorphism in exons 1, 3 or 4, in the context of different HLA-DPA1 (DPA1) polymorphisms (DPA1*01:03 and *02:01). No significant differences in CD4+ T cell allorecognition levels could be demonstrated for any of the beyond exon 2 DPB1 variants studied. Interestingly, however, the mean fold change in CD4+ CD137+ cells was significantly higher when the target shared at least one DPA1 allele with the allogeneic stimulator, compared to a distinct DPA1 background (1.65 vs 0.23, P
| Original language | English |
|---|---|
| Pages (from-to) | 19-29 |
| Number of pages | 11 |
| Journal | Molecular Immunology |
| Volume | 59 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - May 2014 |
Fingerprint
Keywords
- Allorecognition
- HLA-DPA1
- HLA-DPB1
ASJC Scopus subject areas
- Molecular Biology
- Immunology
Cite this
Allorecognition of HLA-DP by CD4+ T cells is affected by polymorphism in its alpha chain. / Lauterbach, Nina; Crivello, Pietro; Wieten, Lotte; Zito, Laura; Groeneweg, Mathijs; Voorter, Christina E M; Fleischhauer, Katharina; Tilanus, Marcel G J.
In: Molecular Immunology, Vol. 59, No. 1, 05.2014, p. 19-29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Allorecognition of HLA-DP by CD4+ T cells is affected by polymorphism in its alpha chain
AU - Lauterbach, Nina
AU - Crivello, Pietro
AU - Wieten, Lotte
AU - Zito, Laura
AU - Groeneweg, Mathijs
AU - Voorter, Christina E M
AU - Fleischhauer, Katharina
AU - Tilanus, Marcel G J
PY - 2014/5
Y1 - 2014/5
N2 - Alloreactivity to HLA-DP molecules, class II heterodimers of an oligomorphic alpha and a polymorphic beta chain, is increasingly being studied due to its relevance in clinical transplantation. We hypothesized that not only polymorphisms in the peptide binding groove encoded by exon 2 of HLA-DPB1, but also in other regions of the molecule and the alpha chain, could play a role in CD4+ T cell allorecognition. To test this possibility, we comparatively investigated CD4+ T cell allorecognition, measured by upregulation of the activation marker CD137, against HLA-DPB1*13:01, *05:01, *03:01, *17:01 or their allele counter parts DPB1*107:01, *135:01, *104:01, *131:01, with identical exon 2 sequences but polymorphism in exons 1, 3 or 4, in the context of different HLA-DPA1 (DPA1) polymorphisms (DPA1*01:03 and *02:01). No significant differences in CD4+ T cell allorecognition levels could be demonstrated for any of the beyond exon 2 DPB1 variants studied. Interestingly, however, the mean fold change in CD4+ CD137+ cells was significantly higher when the target shared at least one DPA1 allele with the allogeneic stimulator, compared to a distinct DPA1 background (1.65 vs 0.23, P
AB - Alloreactivity to HLA-DP molecules, class II heterodimers of an oligomorphic alpha and a polymorphic beta chain, is increasingly being studied due to its relevance in clinical transplantation. We hypothesized that not only polymorphisms in the peptide binding groove encoded by exon 2 of HLA-DPB1, but also in other regions of the molecule and the alpha chain, could play a role in CD4+ T cell allorecognition. To test this possibility, we comparatively investigated CD4+ T cell allorecognition, measured by upregulation of the activation marker CD137, against HLA-DPB1*13:01, *05:01, *03:01, *17:01 or their allele counter parts DPB1*107:01, *135:01, *104:01, *131:01, with identical exon 2 sequences but polymorphism in exons 1, 3 or 4, in the context of different HLA-DPA1 (DPA1) polymorphisms (DPA1*01:03 and *02:01). No significant differences in CD4+ T cell allorecognition levels could be demonstrated for any of the beyond exon 2 DPB1 variants studied. Interestingly, however, the mean fold change in CD4+ CD137+ cells was significantly higher when the target shared at least one DPA1 allele with the allogeneic stimulator, compared to a distinct DPA1 background (1.65 vs 0.23, P
KW - Allorecognition
KW - HLA-DPA1
KW - HLA-DPB1
UR - http://www.scopus.com/inward/record.url?scp=84892841330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892841330&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2013.12.006
DO - 10.1016/j.molimm.2013.12.006
M3 - Article
C2 - 24462895
AN - SCOPUS:84892841330
VL - 59
SP - 19
EP - 29
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 1
ER -