Virus-specific HLA Class II-restricted Cytotoxic T Cells

1986 ◽  
pp. 187-192 ◽  
Author(s):  
Steven Jacobson ◽  
William E. Biddison
1989 ◽  
Vol 63 (4) ◽  
pp. 1756-1762 ◽  
Author(s):  
S Jacobson ◽  
R P Sekaly ◽  
C L Jacobson ◽  
H F McFarland ◽  
E O Long

1998 ◽  
Vol 5 (5) ◽  
pp. 675-682 ◽  
Author(s):  
Kristian Riesbeck ◽  
Anita Billström ◽  
Jesper Tordsson ◽  
Thomas Brodin ◽  
Karin Kristensson ◽  
...  

ABSTRACT The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vβ chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA-primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunotherapy. Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), or the EC line EA.hy926 stimulated with gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) displayed upregulated HLA class II and adhesion molecule (CD54 and CD106) expression, respectively. SEA-primed T cells induced a strong cytotoxicity against IFN-γ- and TNF-α-activated EA.hy926 which had been preincubated with SEA. Blocking of CD54 completely abrogated the T-cell attack. SEA-D227A, which has a mutated class II binding site, did not promote any cytotoxicity. A strong lysis was observed when a fusion protein consisting of protein A and SEA-D227A was added together with T cells to TNF-α-induced EA.hy926 and HUVEC precoated with monoclonal antibodies (MAb) directed against HLA class I, CD54, or CD106 molecules. Finally, an scFv antibody fragment reactive with an unknown EC antigen was fused with SEA-D227A. Both EA.hy926 and HMVEC were efficiently lysed by scFv-SEA-D227A-triggered cytotoxic T cells. Taken together, superantigen-activated T-cell-dependent EC killing was induced when EC expressed an inflammatory phenotype. Moreover, specific MAb targeting of the superantigen to surface antigens induced EC lysis. Our data suggest that directed T-cell-mediated lysis of unwanted proliferating EC, such as those in the tumor microvasculature, can be clinically useful.


1985 ◽  
Vol 13 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Tom H.M. Ottenhoff ◽  
Dienne G. Elferink ◽  
Annemarie Termijtelen ◽  
Frits Koning ◽  
RenéR.P. de Vries
Keyword(s):  
T Cells ◽  
Class Ii ◽  

Science ◽  
1992 ◽  
Vol 255 (5051) ◽  
pp. 1576-1578 ◽  
Author(s):  
D Muller ◽  
B. Koller ◽  
J. Whitton ◽  
K. LaPan ◽  
K. Brigman ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 102-108 ◽  
Author(s):  
M Yasukawa ◽  
T Shiroguchi ◽  
A Inatsuki ◽  
Y Kobayashi

The ability of B-cell chronic lymphocytic leukemia (B-CLL) cells to present antigen to antigen-specific T cells was investigated. B-CLL cells present herpes simplex virus (HSV) antigen and purified protein derivative (PPD) to HSV- and PPD-specific, interleukin-2-dependent T- cell lines in an antigen-specific manner. Treatment of B-CLL cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced markedly increased levels of HLA-DR expression. TPA-treated B-CLL cells showed substantially more effective presentation, especially at low antigen concentrations, than did untreated B-CLL cells. By coculturing different allogeneic combinations of B-CLL cells and T cells and by adding anti-HLA-DR monoclonal antibody to cultures, it was found that antigen presentation by B-CLL cells was restricted by HLA-DR in the same way as for macrophages. We concluded from these experiments that B- CLL cells have a capacity to serve as antigen-presenting cells in an HLA class II-restricted fashion and that increasing the amount of HLA class II antigen and activation of B-CLL cells resulted in effective antigen presentation.


Blood ◽  
2016 ◽  
Vol 128 (17) ◽  
pp. 2165-2174 ◽  
Author(s):  
Cor H. J. Lamers ◽  
Rebecca Wijers ◽  
Cornelis A. M. van Bergen ◽  
Judith A. E. Somers ◽  
Eric Braakman ◽  
...  

Key Points Graft-versus-graft alloreactivity after dUCBT involves recognition of mismatched HLA class II alleles by allele-specific CD4+ effector T cells. Alloreactive donor CD4+ T cells may recognize recipient leukemia if mismatched for individual HLA class II alleles.


1994 ◽  
Vol 180 (1) ◽  
pp. 165-171 ◽  
Author(s):  
K Yamamoto ◽  
Y Fukui ◽  
Y Esaki ◽  
T Inamitsu ◽  
T Sudo ◽  
...  

Studies in vitro have suggested that a species barrier exists in functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecules. However, whether mouse CD4+ T cells restricted by HLA class II molecules are generated in HLA class II transgenic mice and respond to peptide antigens across this barrier has remained unclear. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to influenza hemagglutinin-derived peptide 307-319 (HA 307) and Streptococcus pyogenes M12 protein-derived peptide 347-397 (M6C2), respectively. Inhibition studies with several monoclonal antibodies showed that transgenic HLA class II molecules presented these peptides to mouse CD4+ T cells. Furthermore, T cell lines specific for HA 307 or M6C2 obtained from the transgenic mice could respond to the peptide in the context of relevant HLA class II molecules expressed on mouse L cell transfectants that lack the expression of mouse MHC class II. These findings indicate that interaction between HLA class II and mouse CD4 molecules is sufficient for provoking peptide-specific HLA class II-restricted T cell responses in HLA class II transgenic mice.


Blood ◽  
2009 ◽  
Vol 114 (17) ◽  
pp. 3684-3692 ◽  
Author(s):  
Anita N. Stumpf ◽  
Edith D. van der Meijden ◽  
Cornelis A. M. van Bergen ◽  
Roel Willemze ◽  
J. H. Frederik Falkenburg ◽  
...  

Abstract Potent graft-versus-leukemia (GVL) effects can be mediated by donor-derived T cells recognizing minor histocompatibility antigens (mHags) in patients treated with donor lymphocyte infusion (DLI) for relapsed hematologic malignancies after HLA-matched allogeneic stem cell transplantation (alloSCT). Donor-derived T cells, however, may not only induce GVL, but also mediate detrimental graft-versus-host disease (GVHD). Because HLA-class II is under noninflammatory conditions predominantly expressed on hematopoietic cells, CD4+ T cells administered late after alloSCT may selectively confer GVL without GVHD. Although a broad range of different HLA-class I–restricted mHags have been identified, the first 2 autosomal HLA-class II–restricted mHags have only recently been characterized. By screening a recombinant bacteria cDNA expression library, we identified 4 new HLA-class II–restricted mHags recognized by CD4+ T cells induced in a patient with relapsed chronic myeloid leukemia who achieved long-term complete remission and experienced only mild GVHD of the skin after DLI. All CD4+ T cells were capable of recognizing the mHags presented by HLA-DR surface molecules on primary hematopoietic cells, but not on skin-derived (cytokine-treated) fibroblasts. The selective recognition of hematopoietic cells as well as the balanced population frequencies and common HLA-DR restriction elements make the novel mHags possible targets for development of immunotherapeutic strategies.


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