Recognition of minor histocompatibility antigens on lymphocytic and myeloid leukemic cells by cytotoxic T-cell clones.
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.
van der Harst
D
D
Department of Immunohematology and Bloodbank, University Medical Center, Leiden, The Netherlands.
Goulmy
E
E
Falkenburg
J H
JH
Kooij-Winkelaar
Y M
YM
van Luxemburg-Heijs
S A
SA
Goselink
H M
HM
Brand
A
A
D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D002051:Burkitt Lymphoma / Q000097:blood / Q000276:immunology*; D002999:Clone Cells; D015234:HLA-A Antigens / Q000032:analysis*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000276:immunology*; D007951:Leukemia, Myeloid / Q000097:blood / Q000276:immunology*; D015463:Leukemia, Prolymphocytic / Q000097:blood / Q000276:immunology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D015234:HLA-A Antigens