Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response.
The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A*0201-restricted HY antigen, FIDSYICQV, is a male-specific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8(+) T cells in peripheral blood and molecular remission of relapsed BCR/ABL(+) chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-gamma in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.
Takami
A
A
Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920-8641, Japan. takami@med3.m.kanazawa-u.ac.jp
Sugimori
C
C
Feng
X
X
Yachie
A
A
Kondo
Y
Y
Nishimura
R
R
Kuzushima
K
K
Kotani
T
T
Asakura
H
H
Shiobara
S
S
Nakao
S
S
D000293:Adolescent; D000941:Antigens / Q000737:chemistry; D001752:Blast Crisis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017690:Cell Transplantation; D022801:Complementarity Determining Regions / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D020544:Graft vs Leukemia Effect; D015234:HLA-A Antigens / Q000737:chemistry; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007945:Leukemia, Lymphoid / Q000628:therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000737:chemistry* / Q000276:immunology*; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D022801:Complementarity Determining Regions; D016207:Cytokines; D018076:DNA, Complementary; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D007371:Interferon-gamma