Recognition of minor histocompatibility antigens on lymphocytic and myeloid leukemic cells by cytotoxic T-cell clones

Abstract

Clinical studies indicated an enhanced antileukemic effect of allogeneic bone marrow transplantation (BMT), as compared with autologous BMT. After allogeneic HLA-identical BMT, donor-derived cytotoxic T lymphocytes (CTLs) directed at minor histocompatibility (mH) antigens on the recipients, tissues can be shown. To evaluate the antileukemic reactivity of mH antigen-specific CTLs, we analyzed the expression of mH antigens on circulating lymphocytic and myeloid leukemic cells. We show that the defined mH specificities HA-1 through HA-5 and H-Y are present on leukemic cells, indicating that mH antigen- specific CTLs are capable of HLA class I-restricted antigen-specific lysis of leukemic cells. Compared with interleukin-2-stimulated normal lymphocytes, leukemic cells of lymphocytic origin are less susceptible to T-cell-mediated cytotoxicity by the HA-2 mH antigen-specific CTL and the anti-HLA-A2 CTL clone. A possible explanation for this phenomenon is impaired expression of the LFA-1 adhesion molecule. Our study suggests that mH antigen-specific HLA class I-restricted CD8+ CTLs may be involved in the graft-versus-leukemia reactivity after allogeneic BMT.

Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy

“…mHag polymorphism; and 3) restricted tissue distribution. Moreover, since mHag are clearly expressed on circulating leukemic cells and clonogenic leukemic precursor cells of hoth myeloid and lymphoid origin (164,165). hoth types of leukemias can be targeted.…”

Cytotoxic T‐lymphocyte (CTL) responses against acute or chronic myeloid leukemia

“…In several studies, we have demonstrated that both CD4-and CD8-positive CTL recognizing mH antigens conld be generated in vitro {35, 36,41,42). All mH antigen-specific CD8-positive CTL showed strong lysis of circulating, relatively mature leukemic cells as well as potent antigen-specific cell-mediated suppression or killing of clonogenic leukemic precursor cells (43)(44)(45). Some of the CD4+ clones recognizing mH antigen showed only weak lysis of circulating leukemic cells depending on the density of class II molecules on the cell membrane and the sometimes heterogeneous distribution of class II molecules on the leukemic cell populations (42).…”

Specific depletion of alloreactive T cells in HLA‐identical siblings: a method for separating graft‐versus‐host and graft‐versus‐leukaemia reactions

“…Minor histocompatibility antigen (mHA) differences between patients and their HLA-identical sibling donors are responsible for the alloreactivity causing GVHD and GVL reactions (Barrett & Malkovska, 1996). Leukaemia cells have been shown to express mHAs also present on normal cells (van der Harst et al, 1994). There is some evidence that myeloid leukaemia cells also express two classes of antigen: 'leukaemia-specific' antigens derived from chromosomal translocations, and myeloid-restricted antigens present on leukaemic and normal cells of the myeloid series (Barrett & Malkovska, 1996;Pawelec et al, 1996).…”