Cytotoxic herpes simplex type 2-specific, DQ0602-restricted CD4 T+-cell clones show alloreactivity to DQ0601.
Alloreactivity is one of the most serious problems in organ transplantation. It has been hypothesized that pre-existing alloreactive T cells are actually cross-reacting cells that have been primed by the autologous major histocompatibility complex (MHC) and a specific peptide. CD8+ cytotoxic T lymphocytes that are alloreactive and recognize a virus-peptide that is presented by the autologous MHC have been reported. Here we demonstrate a cross-reactivity that exists between DQ0602 restricted, herpes simplex type 2 VP16 40-50 specific CD4+ T-cell clones, which can be alloreactive to DQ0601. Though most of the DQ0602 restricted T-cell clones we isolated from two different donors were not alloreactive, weakly cross-reacting T-cell clones could be isolated from both donors. Two strongly cross-reacting T-cell clones with high affinity interaction of their T-cell receptor (TCR) with both DQ0602/VP16 40-50 and DQ0601 could be isolated from one donor. DNA sequencing of the a fragment of the Vbeta gene used in their TCR confirmed that these two T cells indeed are two independent clones. These clones are cytotoxic and produce cytokines of a T helper 2-like pattern. Possible implications in a DR-matched transplantation setting are discussed.
Reichstetter
Sandra
S
Research Institute at Virginia Mason, WA 98101, USA.
Standifer
Nathan E
NE
Geubtner
Kelly A
KA
Liu
Andrew W
AW
Agar
Stacy L
SL
Kwok
William W
WW
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
D022801:Complementarity Determining Regions; D016207:Cytokines; D006683:HLA-DQ Antigens; D011948:Receptors, Antigen, T-Cell