title: Dissection and molecular analysis of alloreactive CD8+ T cell responses in allogeneic haematopoietic stem cell transplantation.
abstract: We applied a cDNA expression screening procedure with cryopreserved non-clonal CD8+ T cell populations (Lennerz et al., Proc. Natl. Acad. Sci. USA 102:16013-8, 2005) to the identification of candidate antigens for graft-versus-host disease (GvHD) and graft-versus-leukaemia (GvL) effects in allogeneic haematopoietic stem cell transplantation (allo-HSCT). In a patient-donor model system with HLA class I disparities, we identified an HLA-B*44 mismatch allele, HLA-B*4405, as the dominant target of alloreactive T cells expanded in vitro from donor peripheral blood mononuclear cells (PBMC). HLA-B*4405-reactive T cells were detectable after multiple in vitro stimulations in the patient's post-HSCT PBMC. In a patient-donor model with full HLA compatibility, the major target antigen of donor lymphocytes stimulated in vitro with the respective patient's pre-HSCT PBMC was restricted by HLA-A*0201 and was encoded by TRIM22-442 C, a newly detected polymorphic allele of the tripartite motif family member TRIM22 (synonym: STAF50), preferentially expressed in cells of the haematopoietic system. An arginine(R)-to-cysteine(C) exchange at position 442 generated an immunogenic T cell epitope equivalent to a minor histocompatibility antigen (mHag). TRIM22-442C-specific T cells persisted long-term in the patient's post-HSCT PBMC. Approximately, 1.3% of Caucasians carry TRIM22.442 C in association with HLA-A*0201. In particular, the knowledge of a large and diverse panel of such mHags may be crucial for further improvement of donor selection and adoptive T cell transfer strategies. The procedure applied herein will help to accelerate and facilitate their identification.
authors.affiliation: III. Department of Internal Medicine, Haematology/Oncology, Johannes Gutenberg University, 55101 Mainz, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Wölfel
authors.forename: Volker
authors.initials: V
authors.lastname: Lennerz
authors.forename: Eva
authors.initials: E
authors.lastname: Lindemann
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.forename: Hans G
authors.initials: HG
authors.lastname: Derigs
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
authors.forename: Thomas
authors.initials: T
authors.lastname: Wölfel
mesh_terms: D000328:Adult; D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease; D020544:Graft vs Leukemia Effect; D015235:HLA-B Antigens / Q000737:chemistry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D015778:Minor Histocompatibility Antigens / Q000737:chemistry; D014184:Transplantation, Homologous / Q000379:methods*
chemical_list: D018076:DNA, Complementary; D015235:HLA-B Antigens; D015778:Minor Histocompatibility Antigens