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Article: Monoclonal antibodies that identify the CD3 molecules expressed specifically at the surface of porcine gammadelta-T cells.

Yang, Huaizhi / Parkhouse, R Michael E / Wileman, Thomas

2005 Volume 115, Issue 2, Page(s) 189–196

Abstract: The CD3 antigen is a surface structure associated with the T-cell receptor (TCR) to form a complex ... anti-CD3, these mAb reacted specifically with peripheral gammadelta-T cells, but not with alphabeta ... T cells. Immunoprecipitation showed that the antibody recognized a subset of CD3 molecules that were ...

Abstract	The CD3 antigen is a surface structure associated with the T-cell receptor (TCR) to form a complex involved in antigen recognition and signal transduction. Reports on the structures of the CD3 molecules associated with alphabeta- and gammadelta-TCR have been contradictory. To investigate this issue, we raised a panel of monoclonal antibodies (mAb) against purified porcine CD3 molecules. Unlike the conventional anti-CD3, these mAb reacted specifically with peripheral gammadelta-T cells, but not with alphabeta-T cells. Immunoprecipitation showed that the antibody recognized a subset of CD3 molecules that were associated with gammadelta-TCR. Also unlike the conventional anti-CD3, these mAb, though directed at two different epitope groups, failed to induce antigenic modulation, T-cell proliferation and CD3-redirected cytotoxicity. Taken together, these results suggest that there are differences in the antigenicity, signal transduction potentials and probably structural differences between the CD3 molecules expressed at the surface of alphabeta- and gammadelta-T cells.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; CD3 Complex/immunology ; CD3 Complex/metabolism ; Cell Proliferation ; Female ; Immunophenotyping ; Lymphocyte Activation/immunology ; Male ; Receptors, Antigen, T-Cell, gamma-delta/analysis ; Signal Transduction/immunology ; Swine/immunology ; T-Lymphocyte Subsets/immunology
Chemical Substances	Antibodies, Monoclonal ; CD3 Complex ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2005-04-27
Publishing country	England
Document type	Journal Article
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/j.1365-2567.2005.02137.x
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Article: Coupling of T-cell activation with T-cell receptor assembly.

Terhorst, C / Exley, M / Franco, R / Hall, C / Kang, J / Mueller, B / Sancho, J / She, J / Wileman, T

The Year in immunology

1993 Volume 7, Page(s) 1–24

MeSH term(s)	Amino Acid Sequence ; Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD/physiology ; Cell Adhesion Molecules/physiology ; Humans ; Lymphocyte Activation/physiology ; Mice ; Models, Biological ; Molecular Sequence Data ; Receptor-CD3 Complex, Antigen, T-Cell/immunology ; Receptor-CD3 Complex, Antigen, T-Cell/metabolism ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Signal Transduction ; T-Lymphocyte Subsets/immunology
Chemical Substances	Antigens, CD ; Cell Adhesion Molecules ; Receptor-CD3 Complex, Antigen, T-Cell ; Receptors, Antigen, T-Cell
Language	English
Publishing date	1993
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	632683-3
ISSN	0256-2308
ISSN	0256-2308
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Article: Porcine gammadelta T cells: possible roles on the innate and adaptive immune responses following virus infection.

Takamatsu, H-H / Denyer, M S / Stirling, C / Cox, S / Aggarwal, N / Dash, P / Wileman, T E / Barnett, P V

Veterinary immunology and immunopathology

2006 Volume 112, Issue 1-2, Page(s) 49–61

Abstract: gammadelta T cells recognise different types of antigen in alternative ways to alphabeta T ... cells, and thus appear to play a complementary role in the immune response. However, unlike alphabeta T ... cells, the role or function of gammadelta T cells is still unclear. As pigs possess a high proportion ...

Abstract	gammadelta T cells recognise different types of antigen in alternative ways to alphabeta T cells, and thus appear to play a complementary role in the immune response. However, unlike alphabeta T cells, the role or function of gammadelta T cells is still unclear. As pigs possess a high proportion of circulating gammadelta T cells, they are suitable large animal model to study gammadelta T cell functions. This as yet has not been fully exploited, leaving porcine gammadelta T cell biology and its role in immunity in its infancy. Foot-and-mouth disease (FMD) high potency "emergency" vaccines are able to induce early protection from challenge and it has been suggested that, in part, there is some involvement of innate immune responses. The antigen component of the vaccine is able to stimulate purified naive pig gammadelta T cells and induce the mRNA of various cytokines and chemokines. This observation suggests that gammadelta T cells probably contribute to the early phase of the immune responses to FMD vaccination, and perhaps infection. A subset of these circulating gammadelta T cells display a phenotype similar to professional antigen presenting cells and are able to take up and present soluble antigen to CD4(+) T cells in a direct cell-cell interaction via MHC class II. This direct interaction between gammadelta T cells and CD4(+) T cells is likely to have a significant influence on the out come of the adaptive immune response.
MeSH term(s)	Adaptation, Physiological ; Animals ; Chemokines/genetics ; Cytokines/genetics ; Foot-and-Mouth Disease/immunology ; Foot-and-Mouth Disease/prevention & control ; Immunity, Innate ; Lymphocyte Cooperation ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Swine/immunology ; Swine Diseases/immunology ; T-Lymphocyte Subsets/immunology ; Viral Vaccines/immunology ; Viral Vaccines/pharmacology ; Virus Diseases/immunology ; Virus Diseases/veterinary
Chemical Substances	Chemokines ; Cytokines ; RNA, Messenger ; Receptors, Antigen, T-Cell, gamma-delta ; Viral Vaccines
Language	English
Publishing date	2006-07-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2006.03.011
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Article: Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of Natural Killer, Cytotoxic T, Natural Killer T and MHC un-restricted cytotoxic T-cells

Denyer, M.S / Wileman, T.E / Stirling, C.M.A / Zuber, B / Takamatsu, H.H

Veterinary immunology and immunopathology. 2006 Apr. 15, v. 110, issue 3-4

2006

Abstract: ... and up to 90% were CD3 negative. However, the numbers of perforin positive T-cells increased ... The remaining perforin positive lymphocytes were large and granular and contained more CD3+CD5+CD6+ T-cells (-40 ... lymphocytes, but was not expressed in γδ T-cells or monocyte/macrophages. The perforin positive CD3- subset ...

Abstract	In this study we have used the expression of perforin to characterize subsets of porcine cytotoxic lymphocytes. Perforin positive lymphocytes expressed both CD2 and CD8α, most were small dense lymphocytes (SDL) and up to 90% were CD3 negative. However, the numbers of perforin positive T-cells increased with the age of the animal and their populations increased after specific antigen stimulation in vitro. The remaining perforin positive lymphocytes were large and granular and contained more CD3+CD5+CD6+ T-cells (-40%) of which a substantial proportion also co-expressed CD4. Perforin was expressed in subpopulations of both CD8αα and CD8αβ lymphocytes, but was not expressed in γδ T-cells or monocyte/macrophages. The perforin positive CD3- subset was phenotypically homogeneous and defined as CD5-CD6-CD8β-CD16+CD11b+. This population had NK activity and expressed mRNA for the NK receptor NKG2D, and adaptors DAP10 and DAP12. Perforin positive T-cells (CD3+) could be divided into at least three subsets. The first subset was CD4-CD5+CD6+CD11b-CD16- most were small dense lymphocytes with cytotoxic T-cell activity but not all expressed CD8β. The second subset was mainly observed in the large granular lymphocytes. Their phenotype was CD4+CD5+CD6+CD8β+CD16-CD11b- and also showed functional CTL activity. Thus not all of double positive T-cells are memory helper T-cells. The third subset did not express the T-cell co-receptor CD6, but up to half of them expressed another T-cell co-receptor CD5. The majority of this subset expressed CD11b and CD16, thus the third perforin positive T-cell subset was CD3+CD4-CD5+CD6-CD8β±CD11b+CD16+, and possessed MHC-unrestricted cytotoxicity and LAK activity.
Keywords	swine ; CD8-positive T-lymphocytes ; phenotype ; T-lymphocytes ; cytotoxic T-lymphocytes ; gene expression ; natural killer cells ; major histocompatibility complex ; genetic variation ; messenger RNA ; receptors
Language	English
Dates of publication	2006-0415
Size	p. 279-292.
Document type	Article
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2005.10.005
Database	NAL-Catalogue (AGRICOLA)

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Article: Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of natural killer, cytotoxic T, natural killer T and MHC un-restricted cytotoxic T-cells.

Denyer, Michael S / Wileman, Thomas E / Stirling, Catrina M A / Zuber, Bartek / Takamatsu, Haru-Hisa

Veterinary immunology and immunopathology

2006 Volume 110, Issue 3-4, Page(s) 279–292

Abstract: ... SDL) and up to 90% were CD3 negative. However, the numbers of perforin positive T-cells increased ... The remaining perforin positive lymphocytes were large and granular and contained more CD3+CD5+CD6+ T-cells (-40 ... and CD8alphabeta lymphocytes, but was not expressed in gammadelta T-cells or monocyte/macrophages ...

Abstract	In this study we have used the expression of perforin to characterize subsets of porcine cytotoxic lymphocytes. Perforin positive lymphocytes expressed both CD2 and CD8alpha, most were small dense lymphocytes (SDL) and up to 90% were CD3 negative. However, the numbers of perforin positive T-cells increased with the age of the animal and their populations increased after specific antigen stimulation in vitro. The remaining perforin positive lymphocytes were large and granular and contained more CD3+CD5+CD6+ T-cells (-40%) of which a substantial proportion also co-expressed CD4. Perforin was expressed in subpopulations of both CD8alphaalpha and CD8alphabeta lymphocytes, but was not expressed in gammadelta T-cells or monocyte/macrophages. The perforin positive CD3- subset was phenotypically homogeneous and defined as CD5-CD6-CD8beta-CD16+CD11b+. This population had NK activity and expressed mRNA for the NK receptor NKG2D, and adaptors DAP10 and DAP12. Perforin positive T-cells (CD3+) could be divided into at least three subsets. The first subset was CD4-CD5+CD6+CD11b-CD16- most were small dense lymphocytes with cytotoxic T-cell activity but not all expressed CD8beta. The second subset was mainly observed in the large granular lymphocytes. Their phenotype was CD4+CD5+CD6+CD8beta+CD16-CD11b- and also showed functional CTL activity. Thus not all of double positive T-cells are memory helper T-cells. The third subset did not express the T-cell co-receptor CD6, but up to half of them expressed another T-cell co-receptor CD5. The majority of this subset expressed CD11b and CD16, thus the third perforin positive T-cell subset was CD3+CD4-CD5+CD6-CD8beta+/-CD11b+CD16+, and possessed MHC-unrestricted cytotoxicity and LAK activity.
MeSH term(s)	Animals ; Antigens, CD/metabolism ; Gene Expression Regulation ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Lymphoid Tissue/metabolism ; Major Histocompatibility Complex/immunology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Perforin ; Phenotype ; Pore Forming Cytotoxic Proteins ; Swine/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism
Chemical Substances	Antigens, CD ; Membrane Glycoproteins ; Pore Forming Cytotoxic Proteins ; Perforin (126465-35-8)
Language	English
Publishing date	2006-04-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2005.10.005
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Article: A sub-population of circulating porcine gammadelta T cells can act as professional antigen presenting cells.

Takamatsu, H-H / Denyer, M S / Wileman, T E

Veterinary immunology and immunopathology

2002 Volume 87, Issue 3-4, Page(s) 223–224

Abstract: A sub-population of circulating porcine gammadelta T cells express cell surface antigens associated ... by gammadelta T cells to memory helper T cells was studied by inbred pig lymphocytes immunised with ovalbumin ... lymphocytes still proliferated when stimulated with OVA. When gammadelta T cells were further depleted, OVA ...

Abstract	A sub-population of circulating porcine gammadelta T cells express cell surface antigens associated with antigen presenting cells (APCs), and are able to take up soluble antigen very effectively. Functional antigen presentation by gammadelta T cells to memory helper T cells was studied by inbred pig lymphocytes immunised with ovalbumin (OVA). After removing all conventional APCs from the peripheral blood of immunised pigs, the remaining lymphocytes still proliferated when stimulated with OVA. When gammadelta T cells were further depleted, OVA specific proliferation was abolished, but reconstitution with gammadelta T cells restored proliferation. The proliferation was blocked by monoclonal antibodies (mAb) against MHC class II or CD4, and by pre-treatment of gammadelta T cells with chloroquine. These results indicate that a sub-population of circulating porcine gammadelta T cells act as APCs and present antigen via MHC class II.
MeSH term(s)	Animals ; Antigen-Presenting Cells/physiology ; Lymphocyte Activation ; Ovalbumin/immunology ; Receptors, Antigen, T-Cell, gamma-delta/analysis ; Swine/immunology ; T-Lymphocyte Subsets/physiology
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2002-06-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/s0165-2427(02)00083-1
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Article ; Online: Playing Disability Rugby League with Charcot-Marie-Tooth Disease: A Case Study.

Manny, Luke / Wileman, Taylor / Fornusek, Che / Hackett, Daniel A

Sports (Basel, Switzerland)

2023 Volume 11, Issue 2

Abstract: Charcot-Marie-Tooth (CMT) disease is a common inherited neurological disorder that causes damage to peripheral nerves. Reports of CMT patients participating in team-based sports such as disability rugby league are scarce. The objective of this case ... ...

Abstract	Charcot-Marie-Tooth (CMT) disease is a common inherited neurological disorder that causes damage to peripheral nerves. Reports of CMT patients participating in team-based sports such as disability rugby league are scarce. The objective of this case report was to evaluate the benefits of participation in disability rugby league in a 50-year-old male with CMT. Leg muscle mass and strength was worse for the case subject compared to two age-matched CMT participants with an exercise history; however, evidence of greater function in the case subject was observed through better 6-min walk test performance. Performance in a series of sport specific tests was noticeably worse for the case subject compared to a fellow rugby league player (age matched) with cerebral palsy. Inferior in-game performance was observed for the case subject compared to his fellow rugby league player in terms of distance covered, top running speed, and intensity. However, the case subject may have assumed a different role when playing as evident by the different behaviours he displayed during the games (i.e., less player contacts, tackles, or touches, but more passes of the ball). This case study provides information concerning disability rugby league as an adjunctive mode of treatment for CMT populations.
Language	English
Publishing date	2023-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704239-X
ISSN	2075-4663 ; 2075-4663
ISSN (online)	2075-4663
ISSN	2075-4663
DOI	10.3390/sports11020021
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Article: Evidence for multivalent structure of T-cell antigen receptor complex.

Exley, M / Wileman, T / Mueller, B / Terhorst, C

Molecular immunology

1995 Volume 32, Issue 11, Page(s) 829–839

Abstract: The T-cell antigen receptor (alpha beta or gamma delta TCR) is known to associate with four ... uncertain. We analysed the TCR of a T-T hybridoma which expresses two distinct heterodimers ... with a predicted size of approximately 300 kDa. Taken together, the results suggested that T-cell antigen receptors ...

Abstract	The T-cell antigen receptor (alpha beta or gamma delta TCR) is known to associate with four polypeptides (CD3 gamma, delta, epsilon and zeta) to form the TCR-CD3 complex. Although the six chains are well characterized, the molecular mass of the TCR-CD3 complex and stoichiometry of the components are currently uncertain. We analysed the TCR of a T-T hybridoma which expresses two distinct heterodimers. When the hybridoma was incubated with a mAb (MR9.2) specific for the V alpha 10V beta 5.1 heterodimer, both of the heterodimers were lost from the cell surface, as measured with mAb MR9.2 and MR9.7 (V alpha 1V beta 1-specific). The ability to co-modulate V alpha 1V beta 1 and V alpha 10V beta 5.1 suggested that TCR complexes could contain two alpha beta-heterodimers. Density gradient sedimentation analysis provided further evidence for higher order TCR. The sedimentation patterns of the TCR were compared to that of the B-cell antigen receptor and the well-characterized VSV membrane G-protein as well as to soluble marker proteins. Maximal cell surface murine and human TCR sedimentation coefficients were substantially greater than the 9-10S predicted for a 210 kDa monovalent alpha beta gamma delta epsilon 2 zeta 2 structure. The TCR sedimented in mild non-ionic detergents as large 18 +/- 3S complexes co-migrating with a 443 kDa marker protein. In contrast, the IgM B-cell antigen receptor had a maximal sedimentation coefficient of 10 +/- 3S, consistent with a predicted size of approximately 300 kDa. Taken together, the results suggested that T-cell antigen receptors can contain more than one alpha beta-heterodimer which could be incorporated into a minimal divalent 10-chain TCR-CD3 complex (e.g. alpha beta gamma epsilon epsilon delta zeta zeta alpha beta).
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; CD3 Complex/chemistry ; CD3 Complex/immunology ; Cell Line ; Centrifugation, Density Gradient ; Humans ; Mice ; Receptor Aggregation ; Receptors, Antigen, B-Cell/chemistry ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/immunology
Chemical Substances	CD3 Complex ; Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell
Language	English
Publishing date	1995-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/0161-5890(95)00046-h
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Article: The T cell receptor/T3 complex.

Terhorst, C / de Vries, J / Georgopoulos, K / Gold, D / Oettgen, H / Pettey, C / Spits, H / Ucker, D / van den Elsen, P / Wileman, T

The Year in immunology

1986 Volume 2, Page(s) 245–253

MeSH term(s)	Amino Acid Sequence ; Animals ; Antigen-Presenting Cells/immunology ; Antigens, Surface/immunology ; Base Sequence ; CD3 Complex ; Cell Communication ; Cytotoxicity, Immunologic ; Epitopes/immunology ; Humans ; Immunoglobulin delta-Chains/analysis ; Immunoglobulin delta-Chains/genetics ; Mice ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/physiology ; Receptors, Cell Surface/physiology ; T-Lymphocytes/ultrastructure ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/ultrastructure
Chemical Substances	Antigens, Surface ; CD3 Complex ; Epitopes ; Immunoglobulin delta-Chains ; Receptors, Antigen, T-Cell ; Receptors, Cell Surface
Language	English
Publishing date	1986
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	632683-3
ISSN	0256-2308
ISSN	0256-2308
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Article ; Online: The V-ATPase-ATG16L1 axis recruits LRRK2 to facilitate the lysosomal stress response.

Eguchi, Tomoya / Sakurai, Maria / Wang, Yingxue / Saito, Chieko / Yoshii, Gen / Wileman, Thomas / Mizushima, Noboru / Kuwahara, Tomoki / Iwatsubo, Takeshi

The Journal of cell biology

2024 Volume 223, Issue 3

Abstract: Leucine-rich repeat kinase 2 (LRRK2), a Rab kinase associated with Parkinson's disease and several inflammatory diseases, has been shown to localize to stressed lysosomes and get activated to regulate lysosomal homeostasis. However, the mechanisms of ... ...

Abstract	Leucine-rich repeat kinase 2 (LRRK2), a Rab kinase associated with Parkinson's disease and several inflammatory diseases, has been shown to localize to stressed lysosomes and get activated to regulate lysosomal homeostasis. However, the mechanisms of LRRK2 recruitment and activation have not been well understood. Here, we found that the ATG8 conjugation system regulates the recruitment of LRRK2 as well as LC3 onto single membranes of stressed lysosomes/phagosomes. This recruitment did not require FIP200-containing autophagy initiation complex, nor did it occur on double-membrane autophagosomes, suggesting independence from canonical autophagy. Consistently, LRRK2 recruitment was regulated by the V-ATPase-ATG16L1 axis, which requires the WD40 domain of ATG16L1 and specifically mediates ATG8 lipidation on single membranes. This mechanism was also responsible for the lysosomal stress-induced activation of LRRK2 and the resultant regulation of lysosomal secretion and enlargement. These results indicate that the V-ATPase-ATG16L1 axis serves a novel non-autophagic role in the maintenance of lysosomal homeostasis by recruiting LRRK2.
MeSH term(s)	Adenosine Triphosphatases/metabolism ; Autophagosomes ; Autophagy ; Cell Cycle Proteins ; Lysosomes ; Humans ; Animals ; Mice ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism ; Autophagy-Related Proteins/metabolism
Chemical Substances	Adenosine Triphosphatases (EC 3.6.1.-) ; Cell Cycle Proteins ; LRRK2 protein, human (EC 2.7.11.1) ; ATG16L1 protein, human ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1) ; Autophagy-Related Proteins
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202302067
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