T Cell Reactivity to Human Insulinoma Cell Line (CM) Antigens in Patients with Type 1 Diabetes

Autoimmunity ◽  
1999 ◽  
Vol 29 (3) ◽  
pp. 171-177 ◽  
Author(s):  
L. Monetini ◽  
M. g. Cavallo ◽  
F. Barone ◽  
L. Valente ◽  
M. Russo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Line ◽  
Cell Reactivity ◽  
Insulinoma Cell ◽  
Insulinoma Cell Line ◽  
T Cell Reactivity ◽  
Human Insulinoma

Beta-cell markers and autoantigen expression by a human insulinoma cell line: similarities to native beta cells

1996 ◽  
Vol 150 (1) ◽  
pp. 113-120 ◽  
Author(s):  
M G Cavallo ◽  
F Dotta ◽  
L Monetini ◽  
S Dionisi ◽  
M Previti ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Monoclonal Antibodies ◽  
Beta Cell ◽  
Cell Line ◽  
Beta Cells ◽  
Cell Markers ◽  
Insulinoma Cell ◽  
Insulinoma Cell Line ◽  
Human Insulinoma

Abstract In the present study we have evaluated the expression of different beta-cell markers, islet molecules and autoantigens relevant in diabetes autoimmunity by a human insulinoma cell line (CM) in order to define its similarities with native beta cells and to discover whether it could be considered as a model for studies on immunological aspects of Type 1 diabetes. First, the positivity of the CM cell line for known markers of neuroendocrine derivation was determined by means of immunocytochemical analysis using different anti-islet monoclonal antibodies including A2B5 and 3G5 reacting with islet gangliosides, and HISL19 binding to an islet glycoprotein. Secondly, the expression and characteristics of glutamic acid decarboxylase (GAD) and of GM2-1 ganglioside, both known to be islet autoantigens in diabetes autoimmunity and expressed by human native beta cells, were investigated in the CM cell line. The pattern of ganglioside expression in comparison to that of native beta cells was also evaluated. Thirdly, the binding of diabetic sera to CM cells reacting with islet cytoplasmic antigens (ICA) was studied by immunohistochemistry. The results of this study showed that beta cell markers identified by anti-islet monoclonal antibodies A2B5, 3G5 and HISL-19 are expressed by CM cells; similarly, islet molecules such as GAD and GM2-1 ganglioside are present and possess similar characteristics to those found in native beta cells; the pattern of expression of other gangliosides by CM cells is also identical to human pancreatic islets; beta cell autoantigen(s) reacting with antibodies present in islet cell antibodies (ICA) positive diabetic sera identified by ICA binding are also detectable in this insulinoma cell line. We conclude that CM cells show close similarities to native beta cells with respect to the expression of neuroendocrine markers, relevant beta cell autoantigens in Type 1 diabetes (GAD, GM2-1, ICA antigen), and other gangliosides. Therefore, this insulinoma cell line may be considered as an ideal model for studies aimed at investigating autoimmune phenomena occurring in Type 1 diabetes. Journal of Endocrinology (1996) 150, 113–120

Association of T-cell reactivity with β-cell function in recent onset type 1 diabetes patients

2010 ◽  
Vol 34 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Christian Pfleger ◽  
Guido Meierhoff ◽  
Hubert Kolb ◽  
Nanette C. Schloot
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Function ◽  
Β Cell ◽  
Cell Reactivity ◽  
Recent Onset ◽  
Onset Type ◽  
Β Cell Function ◽  
T Cell Reactivity

T-cell reactivity to 38 kD insulin-secretory-granule protein in patients with recent-onset type 1 diabetes

The Lancet ◽  
1991 ◽  
Vol 337 (8755) ◽  
pp. 1439-1441 ◽  
Author(s):  
B.O. Roep ◽  
A.A. Kallan ◽  
W.L.W. Hazenbos ◽  
R.P. de Vries ◽  
G.J. Bruining ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Secretory Granule ◽  
Cell Reactivity ◽  
Recent Onset ◽  
Onset Type ◽  
Granule Protein ◽  
T Cell Reactivity ◽  
Insulin Secretory Granule

scholarly journals Establishment of T cell lines to bovine beta-casein and beta-casein-derived epitopes in patients with type 1 diabetes

2003 ◽  
Vol 176 (1) ◽  
pp. 143-150 ◽  
Author(s):  
L Monetini ◽  
F Barone ◽  
L Stefanini ◽  
A Petrone ◽  
T Walk ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Beta Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Diabetic Patients ◽  
Beta Casein ◽  
T Cell Lines ◽  
Human Insulinoma

Enhanced cellular immune response to bovine beta-casein has been reported in patients with type 1 diabetes. In this study we aimed to establish beta-casein-specific T cell lines from newly diagnosed type 1 diabetic patients and to characterise these cell lines in terms of phenotype and epitope specificity. Furthermore, since sequence homologies exist between beta-casein and putative beta-cell autoantigens, reactivity to the latter was also investigated. T cell lines were generated from the peripheral blood of nine recent onset type 1 diabetic patients with different HLA-DQ and -DR genotypes, after stimulation with antigen pulsed autologous irradiated antigen presenting cells (APCs) and recombinant human interleukin-2 (rhIL-2). T cell line reactivity was evaluated in response to bovine beta-casein, to 18 overlapping peptides encompassing the whole sequence of beta-casein and to beta-cell antigens, including the human insulinoma cell line, CM, and a peptide from the beta-cell glucose transporter, GLUT-2. T cell lines specific to beta-casein could not be isolated from HLA-matched and -unmatched control subjects. beta-Casein T cell lines reacted to different sequences of the protein, however a higher frequency of T cell reactivity was observed towards the C-terminal portion (peptides B05-14, and B05-17 in 5/9 and 4/9 T cell lines respectively). Furthermore, we found that 1 out of 9 beta-casein-specific T cell lines reacted also to the homologous peptide from GLUT-2, and that 3 out of 4 of tested cell lines reacted also to extracts of the human insulinoma cell line, CM. We conclude that T cell lines specific to bovine beta-casein can be isolated from the peripheral blood of patients with type 1 diabetes; these cell lines react with multiple and different sequences of the protein particularly towards the C-terminal portion. In addition, reactivity of beta-casein T cell lines to human insulinoma extracts and GLUT-2 peptide was detected, suggesting that the potential cross-reactivity with beta-cell antigens deserves further investigation.

T-cell reactivity to 38 kD insulin-secretory granule protein in patients with recent onset type 1 diabetes

1994 ◽  
Vol 17 (7) ◽  
pp. 559-563 ◽  
Author(s):  
B. O. Roep ◽  
A. A. Kallan ◽  
W. L. W. Hazenbos ◽  
J. G. Bruining ◽  
E. M. Bailyes ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Secretory Granule ◽  
Cell Reactivity ◽  
Recent Onset ◽  
Onset Type ◽  
Granule Protein ◽  
T Cell Reactivity ◽  
Insulin Secretory Granule

T-cell reactivity to insulin peptide A1–12 in children with recently diagnosed type 1 diabetes or multiple β-cell autoantibodies

2008 ◽  
Vol 31 (2) ◽  
pp. 142-148 ◽  
Author(s):  
Jane Marttila ◽  
Suvi Huttunen ◽  
Outi Vaarala ◽  
Kunimasa Suzuki ◽  
John F. Elliott ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Β Cell ◽  
Cell Reactivity ◽  
T Cell Reactivity

scholarly journals Mapping T Cell Responses to Native and Neo-Islet Antigen Epitopes in at Risk and Type 1 Diabetes Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Sefina Arif ◽  
Irma Pujol-Autonell ◽  
Yogesh Kamra ◽  
Evangeline Williams ◽  
Norkhairin Yusuf ◽  
...  
Keyword(s):  
At Risk ◽  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Single Cell ◽  
T Cell Responses ◽  
Cell Reactivity ◽  
Cell Responses ◽  
T Cell Reactivity

AimsRecent studies highlight the potentially important role of neoepitopes in breaking immune tolerance in type 1 diabetes. T cell reactivity to these neoepitopes has been reported, but how this response compares quantitatively and phenotypically with previous reports on native epitopes is not known. Thus, an understanding of the relationship between native and neoepitopes and their role as tolerance breakers or disease drivers in type 1 diabetes is required. We set out to compare T cell reactivity and phenotype against a panel of neo- and native islet autoantigenic epitopes to examine how this relates to stages of type 1 diabetes development.MethodsFifty-four subjects comprising patients with T1D, and autoantibody-positive unaffected family members were tested against a panel of neo- and native epitopes by ELISPOT (IFN-γ, IL-10, and IL-17). A further subset of two patients was analyzed by Single Cell Immune Profiling (RNAseq and TCR α/β) after stimulation with pools of native and neoepitope peptides.ResultsT cell responses to native and neoepitopes were present in patients with type 1 diabetes and at-risk subjects, and overall, there were no significant differences in the frequency, magnitude, or phenotype between the two sets of peptide stimuli. Single cell RNAseq on responder T cells revealed a similar profile in T1D patients stimulated with either neo- or native epitopes. A pro-inflammatory gene expression profile (TNF-α, IFN-γ) was dominant in both native and neoepitope stimulated T cells. TCRs with identical clonotypes were found in T cell responding to both native and neoepitopes.Conclusion/InterpretationThese data suggest that in peripheral blood, T cell responses to both native and neoepitopes are similar in terms of frequency and phenotype in patients with type 1 diabetes and high-risk unaffected family members. Furthermore, using a combination of transcriptomic and clonotypic analyses, albeit using a limited panel of peptides, we show that neoepitopes are comparable to native epitopes currently in use for immune-monitoring studies.

T cell reactivity to DR*0401- and DQ*0302-binding peptides of the putative autoantigen IA-2 in type 1 diabetes

2009 ◽  
Vol 107 (03) ◽  
pp. 166-171 ◽  
Author(s):  
T. Lohmann ◽  
T. Halder ◽  
J. Engler ◽  
N. Morgenthaler ◽  
U.-Y. Khoo-Morgenthaler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Reactivity ◽  
Binding Peptides ◽  
T Cell Reactivity
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