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MODERN RHEUMATOLOGY Vol.13 No.3
>MR13-3
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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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