General Discussion: Mycobacterium Leprae Specific Activation of Helper and Suppressor T Cells and its Regulation by HLA Class II Genes and Products

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.

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CD4+ T-cell alloreactivity toward mismatched HLA class II alleles early after double umbilical cord blood transplantation

Blood ◽

10.1182/blood-2016-06-718619 ◽

2016 ◽

Vol 128 (17) ◽

pp. 2165-2174 ◽

Cited By ~ 19

Author(s):

Cor H. J. Lamers ◽

Rebecca Wijers ◽

Cornelis A. M. van Bergen ◽

Judith A. E. Somers ◽

Eric Braakman ◽

...

Keyword(s):

T Cells ◽

Cord Blood Transplantation ◽

Class Ii ◽

Hla Class Ii ◽

Effector T Cells ◽

Cd4 T Cell ◽

Blood Transplantation ◽

Key Points ◽

Allele Specific ◽

Hla Class Ii Alleles

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.

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Functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice.

Journal of Experimental Medicine ◽

10.1084/jem.180.1.165 ◽

1994 ◽

Vol 180 (1) ◽

pp. 165-171 ◽

Cited By ~ 21

Author(s):

K Yamamoto ◽

Y Fukui ◽

Y Esaki ◽

T Inamitsu ◽

T Sudo ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Transgenic Mice ◽

T Cell Responses ◽

Class Ii ◽

Hla Class Ii ◽

Functional Interaction ◽

Leukocyte Antigen ◽

Cell Responses ◽

Hla Class Ii Molecules

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.

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Human Leukocyte Antigen (HLA) Class II Expression on Regulatory T Cells (Tregs) Isolated from Discarded Human Thymus is Induced by In Vitro Expansion Conditions

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2020.01.755 ◽

2020 ◽

Vol 39 (4) ◽

pp. S178-S179

Author(s):

E. Dijke ◽

T. Ellis ◽

I. Larsen ◽

I. Rebeyka ◽

D. Freed ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Human Thymus ◽

In Vitro Expansion

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Identification of 4 new HLA-DR–restricted minor histocompatibility antigens as hematopoietic targets in antitumor immunity

Blood ◽

10.1182/blood-2009-03-208017 ◽

2009 ◽

Vol 114 (17) ◽

pp. 3684-3692 ◽

Cited By ~ 38

Author(s):

Anita N. Stumpf ◽

Edith D. van der Meijden ◽

Cornelis A. M. van Bergen ◽

Roel Willemze ◽

J. H. Frederik Falkenburg ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Hematopoietic Cells ◽

Class Ii ◽

Hla Class Ii ◽

Cdna Expression Library ◽

Expression Library ◽

Histocompatibility Antigens ◽

Minor Histocompatibility Antigens ◽

Hla Dr

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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