tetano
Editor, Senior Moderator
J Immunol. 2014 May 16. pii: 1400343. [Epub ahead of print]
HLA-B27, but Not HLA-B7, Immunodominance to Influenza Is ERAP Dependent.
Akram A1, Lin A2, Gracey E1, Streutker CJ3, Inman RD4.
Author information
Abstract
Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1) plays a critical role in the processing of peptides prior to binding to MHC class I molecules. In this article, we show for the first time, to our knowledge, that the HLA-B27 immunodominant influenza nucleoprotein (NP) 383-391 epitope is made as an N-terminally extended 14-mer before it is trimmed by ERAP. In the absence of ERAP, there is a significant reduction in the CTL response to the B27/NP383-391 epitope in influenza A (flu)-infected B27/ERAP-/- mice. With the use of tetramer staining, the number of naive CD8+ T cells expressing TCR Vβ8.1 in B27/ERAP-/- transgenic mice is significantly lower than that seen in B27/ERAP+/+ mice. HLA-B27 surface expression in naive and flu-infected B27/ERAP-/- mice is also lower than the expression seen for the same allele in naive and flu-infected B27/ERAP+/+ mice. In contrast, surface expression of HLA-B7 was unaffected by the absence of ERAP in B7/ERAP-/- transgenic mice. The B7-restricted NP418-426 CTL response in flu-infected B7/ERAP-/- and B7/ERAP+/+ mice was also similar. These results provide, to our knowledge, the first in vivo demonstration of ERAP functionally influencing host immune response in an HLA allele-specific manner. This principle has relevance to diseases such as ankylosing spondylitis, in which HLA-B27 and ERAP jointly contribute to disease predisposition.
Copyright ? 2014 by The American Association of Immunologists, Inc.
PMID:
24835397
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24835397
HLA-B27, but Not HLA-B7, Immunodominance to Influenza Is ERAP Dependent.
Akram A1, Lin A2, Gracey E1, Streutker CJ3, Inman RD4.
Author information
Abstract
Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1) plays a critical role in the processing of peptides prior to binding to MHC class I molecules. In this article, we show for the first time, to our knowledge, that the HLA-B27 immunodominant influenza nucleoprotein (NP) 383-391 epitope is made as an N-terminally extended 14-mer before it is trimmed by ERAP. In the absence of ERAP, there is a significant reduction in the CTL response to the B27/NP383-391 epitope in influenza A (flu)-infected B27/ERAP-/- mice. With the use of tetramer staining, the number of naive CD8+ T cells expressing TCR Vβ8.1 in B27/ERAP-/- transgenic mice is significantly lower than that seen in B27/ERAP+/+ mice. HLA-B27 surface expression in naive and flu-infected B27/ERAP-/- mice is also lower than the expression seen for the same allele in naive and flu-infected B27/ERAP+/+ mice. In contrast, surface expression of HLA-B7 was unaffected by the absence of ERAP in B7/ERAP-/- transgenic mice. The B7-restricted NP418-426 CTL response in flu-infected B7/ERAP-/- and B7/ERAP+/+ mice was also similar. These results provide, to our knowledge, the first in vivo demonstration of ERAP functionally influencing host immune response in an HLA allele-specific manner. This principle has relevance to diseases such as ankylosing spondylitis, in which HLA-B27 and ERAP jointly contribute to disease predisposition.
Copyright ? 2014 by The American Association of Immunologists, Inc.
PMID:
24835397
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24835397