title: Specificity, degeneracy, and molecular mimicry in antigen recognition by HLA-Class II restricted T cell receptors: implications for clinical medicine.
abstract: 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.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University , 1-1-1 Honjo, Kumamoto 860-8556 , Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uemura
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujii
authors.forename: Leo Kei
authors.initials: LK
authors.lastname: Iwai
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tabata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanai
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Chen
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura