Identification of MHC II-restricted minor histocompatibility antigens after HLA-identical stem-cell transplantation. 2010

Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
Clinical Cooperation Group, Helmholtz-Zentrum München, Munich, Germany.

BACKGROUND After allogeneic hematopoietic stem-cell transplantation (HSCT), donor-derived T cells may elicit graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) responses. The main targets of GVHD and GVT responses after human leukocyte antigen (HLA)-identical HSCT are minor histocompatibility antigens (mHAgs), that is, polymorphic gene products in which recipient and donor differ. Thus, for increasing beneficial GVT and decreasing life-threatening GVHD responses, knowledge of the relevant mHags is required. Here, we sought to identify mHags recognized by CD4 T cells using a novel serologic approach. METHODS To identify candidate mHAgs recognized by CD4 T cells, a cDNA expression library from peripheral blood mononuclear cells of a patient with β-thalassemia major was screened with serum taken at different time points after HLA-identical HSCT. RESULTS Immune responses against 18 antigens were identified with serum taken 100 days posttransplantation, when the patients had recovered from acute GVHD II. Except for one, no humoral responses against these antigens were detected 25 days or 1 year after transplantation. Sequence comparison of these antigens between recipient and donor revealed three polymorphisms of which two were contained within epitopes predicted to bind to HLA-DR molecules of the patient. Using cytokine secretion and capture assays, T cells specific for the polymorphic antigens of the recipient, but not the donor, were isolated from peripheral blood monocyte cells after HSCT. CONCLUSIONS The serologic approach described here facilitates the rapid identification of mHAgs recognized by CD4 T cells. Furthermore, the correlation of humoral and cellular immune responses with acute GVHD implies a role of these antigens in GVHD pathology.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D006086 Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006650 Histocompatibility Testing Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed) Crossmatching, Tissue,HLA Typing,Tissue Typing,Crossmatchings, Tissue,HLA Typings,Histocompatibility Testings,Testing, Histocompatibility,Testings, Histocompatibility,Tissue Crossmatching,Tissue Crossmatchings,Tissue Typings,Typing, HLA,Typing, Tissue,Typings, HLA,Typings, Tissue
D006680 HLA Antigens Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases. Human Leukocyte Antigen,Human Leukocyte Antigens,Leukocyte Antigens,HL-A Antigens,Antigen, Human Leukocyte,Antigens, HL-A,Antigens, HLA,Antigens, Human Leukocyte,Antigens, Leukocyte,HL A Antigens,Leukocyte Antigen, Human,Leukocyte Antigens, Human
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000949 Histocompatibility Antigens Class II Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen. Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D014019 Tissue Donors Individuals supplying living tissue, organs, cells, blood or blood components for transfer or transplantation to histocompatible recipients. Organ Donors,Donors,Ovum Donors,Semen Donors,Transplant Donors,Donor,Donor, Organ,Donor, Ovum,Donor, Semen,Donor, Tissue,Donor, Transplant,Donors, Organ,Donors, Ovum,Donors, Semen,Donors, Tissue,Donors, Transplant,Organ Donor,Ovum Donor,Semen Donor,Tissue Donor,Transplant Donor
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte

Related Publications

Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
January 1992, International immunology,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
January 2016, Bone marrow transplantation,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
July 2004, Vox sanguinis,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
September 2003, Experimental hematology,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
March 1986, Immunology today,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
December 2005, Haematologica,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
June 2007, Best practice & research. Clinical haematology,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
July 2008, Deutsche medizinische Wochenschrift (1946),
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
October 2009, Blood,
Slavoljub Milosevic, and Barbara Bachnick, and Karzan Karim, and Georg W Bornkamm, and Klaus Witter, and Armin Gerbitz, and Josef Mautner, and Uta Behrends
March 2012, DNA and cell biology,
Copied contents to your clipboard!