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Concurrent detection of circulating minor histocompatibility antigen-specific CD8+ T cells in SCT recipients by combinatorial encoding MHC multimers.

Broen, Kelly and Greupink-Draaisma, Annelies and Woestenenk, Rob and Schaap, Nicolaas and Brickner, Anthony G and Dolstra, Harry (2011) Concurrent detection of circulating minor histocompatibility antigen-specific CD8+ T cells in SCT recipients by combinatorial encoding MHC multimers. PLoS One, 6 (6). e21266 - ?.

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Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematologic malignancies. Its therapeutic effect is largely dependent on recognition of minor histocompatibility antigens (MiHA) by donor-derived CD8⁺ T cells. Therefore, monitoring of multiple MiHA-specific CD8⁺ T cell responses may prove to be valuable for evaluating the efficacy of allogeneic SCT. In this study, we investigated the use of the combinatorial encoding MHC multimer technique to simultaneously detect MiHA-specific CD8⁺ T cells in peripheral blood of SCT recipients. Feasibility of this approach was demonstrated by applying dual-color encoding MHC multimers for a set of 10 known MiHA. Interestingly, single staining using a fluorochrome- and Qdot-based five-color combination showed comparable results to dual-color staining for most MiHA-specific CD8⁺ T cell responses. In addition, we determined the potential value of combinatorial encoding MHC multimers in MiHA identification. Therefore, a set of 75 candidate MiHA peptides was predicted from polymorphic genes with a hematopoietic expression profile and further selected for high and intermediate binding affinity for HLA-A2. Screening of a large cohort of SCT recipients resulted in the detection of dual-color encoded CD8⁺ T cells following MHC multimer-based T cell enrichment and short ex vivo expansion. Interestingly, candidate MiHA-specific CD8⁺ T cell responses for LAG3 and TLR10 derived polymorphic peptides could be confirmed by genotyping of the respective SNPs. These findings demonstrate the potency of the combinatorial MHC multimer approach in the monitoring of CD8⁺ T cell responses to known and potential MiHA in limited amounts of peripheral blood from allogeneic SCT recipients.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Broen, Kelly
Greupink-Draaisma, Annelies
Woestenenk, Rob
Schaap, Nicolaas
Brickner, Anthony Gagb10@pitt.eduAGB10
Dolstra, Harry
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 26 May 2011
Date Type: Acceptance
Journal or Publication Title: PLoS One
Volume: 6
Number: 6
Page Range: e21266 - ?
DOI or Unique Handle: 10.1371/journal.pone.0021266
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
Uncontrolled Keywords: Amino Acid Sequence, CD8-Positive T-Lymphocytes, Cell Proliferation, Enzyme-Linked Immunosorbent Assay, Epitopes, Humans, Lymphocyte Count, Major Histocompatibility Complex, Minor Histocompatibility Antigens, Molecular Sequence Data, Peptides, Protein Multimerization, Staining and Labeling, Stem Cell Transplantation, Tissue Donors
Funders: NCI NIH HHS (R01 CA118880-05), NCI NIH HHS (R01CA118880), NCI NIH HHS (R01 CA118880-01A1), NCI NIH HHS (R01 CA118880-04), NCI NIH HHS (R01 CA118880-03), NCI NIH HHS (R01 CA118880), NCI NIH HHS (R01 CA118880-02)
MeSH Headings: Amino Acid Sequence; CD8-Positive T-Lymphocytes--cytology; CD8-Positive T-Lymphocytes--immunology; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Epitopes; Humans; Lymphocyte Count; Major Histocompatibility Complex--immunology; Minor Histocompatibility Antigens--blood; Molecular Sequence Data; Peptides--chemistry; Peptides--immunology; Protein Multimerization--immunology; Staining and Labeling--methods; Stem Cell Transplantation; Tissue Donors
Other ID: NLM PMC3123304
PubMed Central ID: PMC3123304
PubMed ID: 21731686
Date Deposited: 05 Sep 2012 17:42
Last Modified: 30 Oct 2017 23:58


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