Refinement of molecular approaches to improve the chance of identification of hematopoietic-restricted minor histocompatibility antigens.

Fulltext:
71202.pdf
Embargo:
until further notice
Size:
1.076Mb
Format:
PDF
Description:
publisher's version
Publication year
2008Source
Journal of Immunological Methods, 329, 1-2, (2008), pp. 125-37ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
CHL
Rheumatology
Haematology
Journal title
Journal of Immunological Methods
Volume
vol. 329
Issue
iss. 1-2
Page start
p. 125
Page end
p. 37
Subject
IGMD 7: Iron metabolism; NCMLS 2: Immune Regulation; ONCOL 3: Translational research; UMCN 1.4: Immunotherapy, gene therapy and transplantationAbstract
Minor histocompatibility antigens (mHAgs) constitute the target antigens of the T cell-mediated graft-versus-leukemia response after HLA-identical allogeneic stem cell transplantation (SCT). Several human mHAgs have been identified, but only a few are selectively expressed by hematopoietic cells representing potential targets for specific immunotherapy. Molecular approaches including cDNA library screening and genetic linkage analysis have been successfully applied to identify T cell-defined mHAgs, but each approach has its drawbacks which may lead to mis-identification of the mHAg of interest. We improved both molecular strategies to facilitate more robust identification of hematopoietic-restricted mHAgs. First, we adapted cDNA library cloning by using 293T cells with stable expression of the relevant MHC class I allele, CD80 and CD54. We demonstrated that cDNA library screening using this 293T expression system results in strong activation of cytotoxic T lymphocytes, which significantly contributes to improvement of the assay sensitivity. Second, we refined genetic linkage analysis using single nucleotide polymorphism (SNP) genotyping to narrow down the defined genetic region that holds the mHAg-encoding gene. We showed that SNP marker analysis provides additional information about the genetic position of the antigen-encoding gene. Application of these optimized molecular approaches will lead to more rapid and reliable molecular identification of hematopoietic-restricted mHAgs.
This item appears in the following Collection(s)
- Academic publications [227864]
- Electronic publications [107316]
- Faculty of Medical Sciences [86218]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.