Alloreactive T Cell Responses Between Hla-Identical Siblings

Irlé, C; Pg, Beatty; Mickelson, Eric; Ed, Thomas; Ja, Hansen

doi:10.1097/00007890-198509000-00021

Cited by 34 publications

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“…In human GvHD, host antigen-specific cytotoxic Tcells (CTL) are considered to be the local effectors because of an inverse CD4/CD8 T cell ratio in the epithelial target organs and the presence of characteristic -target cell conjugates within GvHD-affected tissues such as the epidermal tissue of the skin [12, 131. It is well established that host-reactive CTL are present in the peripheral blood of patients suffering from acute or chronic GvHD upon grafting with MHC genotypically identical BM [14][15][16][17]. These host-specific CTL were generally found to exert class I MHC restricted recognition of [I 96221 polymorphic non-MHC antigens, or minor histocompatibility (mH) antigens [14-171.…”

Section: Introductionmentioning

confidence: 99%

Minor histocompatibility antigens, defined by graft‐vs.‐host disease‐derived cytotoxic T lymphocytes, show variable expression on human skin cells

et al. 1991

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Little is known on the effector mechanisms inducing the cutaneous lesions observed during acute graft-vs.-host disease (aGvHD) after allogeneic bone marrow transplantation (BMT). Histological findings have indicated that infiltrating CD8+ lymphocytes probably play a role. We addressed the question of whether host minor histocompatibility (mH) antigen-reactive cytotoxic T lymphocytes (CTL) could account for this phenomenon via direct lysis of the epidermal cell layer. Six CTL clones, obtained from peripheral blood lymphocytes of patients suffering from aGvHD, each recognizing a well-characterized MHC class I-restricted mH antigen epitope, were tested on cultured keratinocytes of nine MHC and mH antigen-typed donors. Four of six mH antigen-specific CTL clones lysed unstimulated MHC class I-expressing, as well as recombinant interferon-gamma (rIFN-gamma)-activated, ICAM-1, MHC class I- and II-expressing keratinocytes. Two strongly cytolytic CTL clones showed no recognition of keratinocytes of donors whose phytohemagglutinin-activated T cell lines were readily lysed. With respect to a GvHD, the results imply that some class I-restricted CTL obtained from peripheral blood lymphocytes of a GvHD patients have the in vitro potential to destroy resting as well as IFN-gamma-activated epidermal cells, whereas others do not. In other words, CTL-defined human mH antigens vary with respect to their expression in the skin. It is intriguing that those minor H antigens which cannot be detected on human keratinocytes in vitro are those known to be associated with the occurrence of GvHD.

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Section: Introductionmentioning

confidence: 99%

Minor histocompatibility antigens, defined by graft‐vs.‐host disease‐derived cytotoxic T lymphocytes, show variable expression on human skin cells

et al. 1991

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“…Hmy2CIR cells expressing this chimeric antigen were not killed by the hmHA-1-specific CTL clones (Fig. 4) lines (2,3,7,13), or putative "CTL clones" with low lytic activities (8). Therefore, establishment of hmHA-specific CTL clones and delineation of their specificities as well as restriction elements by using such clones have been needed for the advancement of clinical transplantation.…”

Section: Resultsmentioning

confidence: 99%

“…Other hmHAs were also detected by CTLs (2,(4)(5)(6)(7)(8). As in the mouse, responses of these CTLs were restricted by major histocompatibility complex class I antigens.…”

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confidence: 87%

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Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules.

Yamamoto

Kariyone

Akiyama

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister 2 (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1-specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null CTLs (3,[9][10][11][12]. Other hmHAs were also detected by CTLs (2, 4-8). As in the mouse, responses of these CTLs were restricted by major histocompatibility complex class I antigens. Only a limited number of HLA allospecificities have been reported as restriction molecules in the recognition of hmHAs. Among them, HLA-A2 and -B7 were two major ones, although there are examples of restriction by 13). These studies strongly suggested that certain HLA-A/B molecules can present hmHAs to T cells.In the present study, we attempted to generate CTL clones recognizing hmHAs from a recipient of multiple renal grafts and to characterize in detail CTL clones and corresponding hmHAs. Furthermore, the restriction elements in the CTL recognition of hmHAs were investigated by using Hmy2CIR cells transfected with HLA class I genes.MATERIALS AND METHODS Cells. B cells from the patient and the second donor (sister 3; S3 in Fig. 1) were transformed by Epstein-Barr virus (EBV). These transformed B-cell lines were grown in RPMI 1640 medium supplemented with 2 mM L-glutamine and 10% (vol/vol) fetal calf serum. EBV-transformed cell lines HVB-B5, LeolO, FS, CRB-087B, JBUSH, and AMAI were kindly supplied by F. Otani (Kitasato University, Kanagawa, Japan) and grown in the same medium. Peripheral blood lymphocytes (PBL) from six healthy staff members (Sug, YO, KT, YK, ST, and Tm) as well as those from the father, mother, sister 2 (S2), and S3 of the patient were stimulated twice by 0.2% phytohemagglutinin (PHA; Difco). The PHA-induced T cells were used as target cells for the CTL assay.Hmy2CIR cells expressing HLA-B35, -B51, or -Bw52 antigens or HLA-B51/35 chimeric antigens were previously generated (14-16). The HLA-Bw53 genomic gene has been cloned and transfected into Hmy2CIR cells (unpublished data). These cells were grown in the same medium supplemented with hygromycin B (0.2 mg/ml). Untransfected Hmy2CIR cells were grown in the medium without hygromycin B.Antibodies. W6/32 (17) and ME40.5 (18) HLA class I monomorphic, L243 HLA-DR monomorphic (19), antiLeu-10 HLA-DQ monomorphic (20), B7/21 HLA-DP monomorphic (21), OKT3 anti-human CD3 (22), OKT8 anti-human CD8 (22), OKT4 anti-human CD4 (22), and WT31 anti-human a,,3 T-cell re...

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“…The expression of mouse mH peptides was dependent on coexpression of the restricting MHC class I molecule [27]. On the other hand, the tissue distribution of hmH antigen is not well studied.To date, the expression of hmH antigen has only been reported on hematopoietic progenitor cells [7] and keratinocytes [8] in addition to mature T and Bcells. This study provides additional information about the tissue distribution of hmH antigen on kidney cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of human minor histocompatibility antigen on cultured kidney cells

et al. 1993

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Incompatibility of human minor histocompatibility (hmH) antigens can induce rejection of grafts in organ transplantation and graft-versus-host reactions in bone marrow transplantation. In spite of their importance in clinical transplantation, hmH antigens are not well studied. Previous studies have demonstrated the expression of hmH antigens on T and B cells, hematopoietic progenitor cells and keratinocytes. We have for the first time demonstrated the expression of hmH antigens on cultured kidney cells using HLA-B35-restricted, hmH antigen-specific cytotoxic T lymphocyte (CTL) clones, which were previously established from a patient who rejected two kidneys from HLA-identical sisters. The CTL clones could not kill cultured kidney cells. Since cultured kidney cells expressed very low levels of HLA class I antigens it was thought that their failure to be killed by the CTL clones was due to lack of expression of HLA-B35 antigens. After induction of class I antigens on cultured kidney cells by interferon-gamma (IFN-gamma), the IFN-gamma-treated cultured kidney cells were killed by the CTL clones. Furthermore, we isolated hmH antigens as peptides from cultured kidney cells after treatment with IFN-gamma. These results indicate that cultured kidney cells express hmH antigens when HLA class I antigen is induced by IFN-gamma and hmH antigens on cultured kidney cells are recognized by T cells as peptides presented by HLA-B35 molecules.

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Alloreactive T Cell Responses Between Hla-Identical Siblings

Cited by 34 publications

References 0 publications

Minor histocompatibility antigens, defined by graft‐vs.‐host disease‐derived cytotoxic T lymphocytes, show variable expression on human skin cells

Minor histocompatibility antigens, defined by graft‐vs.‐host disease‐derived cytotoxic T lymphocytes, show variable expression on human skin cells

Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules.

Expression of human minor histocompatibility antigen on cultured kidney cells

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