Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response.

Abstract

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.

• Authors: A Takami, C Sugimori, X Feng, A Yachie, Y Kondo, R Nishimura, K Kuzushima, T Kotani, H Asakura, S Shiobara, S Nakao
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 34 Issue 8 Pg. 703-9 (Oct 2004) ISSN: 0268-3369 [Print] England
• PMID: 15322566 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens
• Complementarity Determining Regions
• Cytokines
• DNA, Complementary
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Minor Histocompatibility Antigens
• Peptides
• Interferon-gamma

Topics

• Adolescent
• Antigens (chemistry)
• Blast Crisis
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cell Transplantation
• Complementarity Determining Regions (chemistry)
• Cytokines (biosynthesis)
• DNA, Complementary (metabolism)
• Dose-Response Relationship, Drug
• Female
• Flow Cytometry
• Graft vs Leukemia Effect
• HLA-A Antigens (chemistry)
• HLA-A2 Antigen
• Humans
• Interferon-gamma (biosynthesis)
• Leukemia, Lymphoid (therapy)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (metabolism)
• Male
• Minor Histocompatibility Antigens (chemistry, immunology)
• Peptides (chemistry)
• Polymerase Chain Reaction
• Sex Factors
• T-Lymphocytes (immunology, metabolism)