Isolation of human CD4/CD8 double-positive, graft-versus-host disease-protective, minor histocompatibility antigen-specific regulatory T cells and of a novel HLA-DR7-restricted HY-specific CD4 clone.

Abstract

Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4(+)/CD8(+) double-positive; 2) specific for an HLA class I-restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I-restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7-restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease-protective, minor H Ag-specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.

• Authors: Assia Eljaafari, Ozel Yuruker, Christophe Ferrand, Annie Farre, Caroline Addey, Marie-Laure Tartelin, Xavier Thomas, Pierre Tiberghien, Elizabeth Simpson, Dominique Rigal, Diane Scott
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 190 Issue 1 Pg. 184-94 (Jan 01 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 23225889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• H-Y Antigen
• HLA-DR7 Antigen
• HLA-DRB1 Chains
• Minor Histocompatibility Antigens

Topics

• Antigen Presentation (immunology)
• CD4-Positive T-Lymphocytes (cytology, immunology, metabolism)
• CD8-Positive T-Lymphocytes (cytology, immunology, metabolism)
• Cell Line, Transformed
• Cell Separation (methods)
• Clone Cells
• Epitopes, T-Lymphocyte (immunology)
• Female
• Graft vs Host Disease (immunology, pathology, prevention & control)
• H-Y Antigen (immunology)
• HLA-DR7 Antigen (genetics)
• HLA-DRB1 Chains (genetics)
• Humans
• Male
• Minor Histocompatibility Antigens (immunology, metabolism)
• T-Lymphocytes, Regulatory (cytology, immunology, metabolism)