Citrulline-containing myelin basic protein is recognized by T-cell lines derived from multiple sclerosis patients and healthy individuals

Neurology ◽  
1994 ◽  
Vol 44 (1) ◽  
pp. 123-123 ◽  
Author(s):  
R. Martin ◽  
J. N. Whitaker ◽  
L. Rhame ◽  
R. R. Goodin ◽  
H. F. McFarland



1994 ◽  
Vol 49 (1-2) ◽  
pp. 45-50 ◽  
Author(s):  
Yuan K. Chou ◽  
Richard E. Jones ◽  
Dennis Bourdette ◽  
Ruth Whithman ◽  
George Hashim ◽  
...  


2001 ◽  
Vol 123 (2) ◽  
pp. 288-293 ◽  
Author(s):  
D. Montanaro ◽  
V. Sanna ◽  
G. Matarese ◽  
B. B. Larby ◽  
L Racioppi ◽  
...  


1993 ◽  
Vol 13 (2) ◽  
pp. 152-161 ◽  
Author(s):  
Yufen Qin ◽  
Stanley van den Noort ◽  
Jeff Kurt ◽  
Sudhir Gupta


1994 ◽  
Vol 179 (3) ◽  
pp. 973-984 ◽  
Author(s):  
J Zhang ◽  
S Markovic-Plese ◽  
B Lacet ◽  
J Raus ◽  
H L Weiner ◽  
...  

Equal numbers of CD4+ T cells recognizing myelin basic protein (MBP) and proteolipid protein (PLP) are found in the circulation of normal individuals and multiple sclerosis (MS) patients. We hypothesized that if myelin-reactive T cells are critical for the pathogenesis of MS, they would exist in a different state of activation as compared with myelin-reactive T cells cloned from the blood of normal individuals. This was investigated in a total of 62 subjects with definitive MS. While there were no differences in the frequencies of MBP- and PLP-reactive T cells after primary antigen stimulation, the frequency of MBP or PLP but not tetanus toxoid-reactive T cells generated after primary recombinant interleukin (rIL-2) stimulation was significantly higher in MS patients as compared with control individuals. Primary rIL-2-stimulated MBP-reactive T cell lines were CD4+ and recognized MBP epitopes 84-102 and 143-168 similar to MBP-reactive T cell lines generated with primary MBP stimulation. In the cerebrospinal fluid (CSF) of MS patients, MBP-reactive T cells generated with primary rIL-2 stimulation accounted for 7% of the IL-2-responsive cells, greater than 10-fold higher than paired blood samples, and these T cells also selectively recognized MBP peptides 84-102 and 143-168. In striking contrast, MBP-reactive T cells were not detected in CSF obtained from patients with other neurologic diseases. These results provide definitive in vitro evidence of an absolute difference in the activation state of myelin-reactive T cells in the central nervous system of patients with MS and provide evidence of a pathogenic role of autoreactive T cells in the disease.



2000 ◽  
Vol 6 (4) ◽  
pp. 220-225 ◽  
Author(s):  
Laura R Tranquill ◽  
Ligong Cao ◽  
Nicholas C Ling ◽  
Hubert Kalbacher ◽  
Roland M Martin ◽  
...  

Myelin basic protein (MBP), a candidate autoantigen in multiple sclerosis (MS), exists in different isoforms and charge isomers generated by differential splicing of exons and by a combination of posttranslational modifications, respectively. These various isoforms and charge isomers of MBP vary in abundance and most likely serve different functions during myelinogenesis and remyelination. The least cationic among the charge isomers of MBP is citrullinated and is referred to as MBP-C8. MBP-C8 is relatively increased in the population of MBP isomers in more developmentally immature myelin and in MS brain tissue. In a previous study, we found that MBP-C8-reactive T cells could be detected in CD4+ T cell lines (TCL) generated with MBP from both MS patients and normal controls. Here, we examined the frequency and peptide specificity of MBPC8-specific TCL generated with MBP-C8 in MS patients and controls. Ten subjects grouped in five sets, each an MS patient and a control, were studied. In all cases, the MS patient had either a higher overall number of MBP-C8-responding lines, responded with greater sensitivity to the MBPC8 antigen or both. Few lines responded to the MBP-C8 peptides but, if they did, they appeared to be specific to the carboxyl-half of the MBP-C8 molecule. Given the large amounts of citrullinated MBP in MS brain tissue, a preferential T cell response to MBP-C8 may be involved in the induction and perpetuation of this disease.



1993 ◽  
Vol 14 (2) ◽  
pp. 139-143 ◽  
Author(s):  
G. Ristori ◽  
M. Salvetti ◽  
C. Buttinelli ◽  
M. Falcone ◽  
S. Trabace ◽  
...  


1992 ◽  
Vol 139 (1) ◽  
pp. 118-130 ◽  
Author(s):  
Zhang Jingwu ◽  
Marleen Schreurs ◽  
Robert Medaer ◽  
Jef C.M. Raus


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