Identification of biological relevant minor histocompatibility antigens within the b-lymphocyte–derived hla-ligandome using a reverse immunology approach
P Hombrink, C Hassan, MGD Kester, L Jahn… - Clinical Cancer …, 2015 - AACR
P Hombrink, C Hassan, MGD Kester, L Jahn, MJ Pont, AH de Ru, CAM van Bergen…
Clinical Cancer Research, 2015•AACRPurpose: T-cell recognition of minor histocompatibility antigens (MiHA) not only plays an
important role in the beneficial graft-versus-leukemia (GVL) effect of allogeneic stem cell
transplantation (allo-SCT) but also mediates serious GVH complications associated with allo-
SCT. Using a reverse immunology approach, we aim to develop a method enabling the
identification of T-cell responses directed against predefined antigens, with the goal to select
those MiHAs that can be used clinically in combination with allo-SCT. Experimental Design …
important role in the beneficial graft-versus-leukemia (GVL) effect of allogeneic stem cell
transplantation (allo-SCT) but also mediates serious GVH complications associated with allo-
SCT. Using a reverse immunology approach, we aim to develop a method enabling the
identification of T-cell responses directed against predefined antigens, with the goal to select
those MiHAs that can be used clinically in combination with allo-SCT. Experimental Design …
Abstract
Purpose: T-cell recognition of minor histocompatibility antigens (MiHA) not only plays an important role in the beneficial graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (allo-SCT) but also mediates serious GVH complications associated with allo-SCT. Using a reverse immunology approach, we aim to develop a method enabling the identification of T-cell responses directed against predefined antigens, with the goal to select those MiHAs that can be used clinically in combination with allo-SCT.
Experimental Design: In this study, we used a recently developed MiHA selection algorithm to select candidate MiHAs within the HLA-presented ligandome of transformed B cells. From the HLA-presented ligandome that predominantly consisted of monomorphic peptides, 25 polymorphic peptides with a clinically relevant allele frequency were selected. By high-throughput screening, the availability of high-avidity T cells specific for these MiHA candidates in different healthy donors was analyzed.
Results: With the use of MHC multimer enrichment, analyses of expanded T cells by combinatorial coding MHC multimer flow cytometry, and subsequent single-cell cloning, positive T-cell clones directed to two new MiHA: LB-CLYBL-1Y and LB-TEP1-1S could be demonstrated, indicating the immunogenicity of these two MiHAs.
Conclusions: The biologic relevance of MiHA LB-CLYBL-1Y was demonstrated by the detection of LB-CLYBL-1Y–specific T cells in a patient suffering from acute myeloid leukemia (AML) that experienced an anti-leukemic response after treatment with allo-SCT. Clin Cancer Res; 21(9); 2177–86. ©2015 AACR.
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