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MR Vol.13 No.3 indexに戻る
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MODERN RHEUMATOLOGY
Vol.13 No.3 |
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Specificity, degeneracy, and molecular
mimicry in antigen recognition by HLA-Class II restricted T cell
receptors: implications for clinical medicine
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| Yasushi Uemura1, Satoru Senju1, Shinji Fujii1,
2, Leo Kei Iwai1, 4, Katsumi Maenaka5, Hiroki Tabata1, 3, Takayuki
Kanai1, Yu-Zhen Chen1 and Yasuharu Nishimura1 |
(1) Department of Immunogenetics, Graduate School
of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto,
860-8556, Japan
(2) Department of Respiratory Medicine, Kumamoto University School of Medicine,
Kumamoto, Japan
(3) Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto,
Japan
(4) Laboratory of Immunology, Heart Institute (Incor), University of Sao Paulo
Medical School, Sao Paulo, Brazil
(5) Division of Structural Biology, Medical Institute of Bioregulation, Kyushu
University, Fukuoka, Japan |
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| Received: 05 December 2002 Accepted: 10 February
2003 |
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| Abstract |
| In humans, increased susceptibility to specific
autoimmune diseases is closely associated with specific HLA-class
II alleles. CD4+ T cells that recognize short self-peptides in the
context of HLA-class II molecules via their T cell receptor (TCR)
are considered to mediate the central role of pathogenesis in autoimmunity.
Although both self- and nonself-peptides are presented on HLA-class
II molecules under physiological conditions, several mechanisms exist
to avoid the T cell response to the self-peptide/HLA-class II complex.
One of the mechanisms that account for the breakdown in immune tolerance
is cross-recognition by TCR between a pathogen-derived antigen and
a host antigen (molecular mimicry theory). Epidemiological studies
have indicated that a number of autoimmune diseases are developed
or exacerbated after infections. Therefore, elucidating the recognition
nature of HLA-class II restricted TCR in detail is necessary in order
to understand disease processes. A large body of evidence indicates
that T cell recognition is highly degenerate, and many different
peptides can activate an individual T cell. Degeneracy of TCR recognition
also can appear in various physiological outcomes, ranging from full
activation to strong antagonism. Here, we review the clinical implications
of our findings on T cell recognition, as well as a new direction
of future applications for analyses in molecular mimicry. We also
describe the latest developments in methods of mapping TCR epitopes
for CD4+ T cells using a peptide epitope expression library generated
in the class II-associated invariant chain peptide substituted invariant
chain gene format. |
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| Key words |
| Autoimmunity - Epitopes - HLA - Molecular mimicry
- T cell receptors (TCR) |
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