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  • Title: TCR diversity of H60-specific CD8 T cells during the response evolution and influence of CD4 help.
    Author: Choi JH, Ryu SJ, Jung KM, Kim S, Chang J, Kim TW, Choi EY.
    Journal: Transplantation; 2009 Jun 15; 87(11):1609-16. PubMed ID: 19502951.
    Abstract:
    BACKGROUND: H60 is a hematopoietic cell-specific dominant minor histocompatibility antigen that is considered to be ideal for modeling leukemia treatment after bone-marrow transplantation. We characterized the H60-specific CD8 T-cell response as CD4 help dependent. This study investigated the T-cell receptor (TCR) repertoires during the evolution of H60-specific CD8 T-cell responses and influence of CD4 help on the diversity. METHODS: Ex vivo TCR V beta and complementarity-determining region 3 length spectratypic and clonotypic analyses were performed using H60-tetramer-binding CD8 T cells purified from the mice undergoing the primary, secondary, and tertiary responses with cognate help, and the secondary response with noncognate separate CD4 help. RESULTS: Involvement of a broad spectrum of TCRs was observed in the H60-specific primary response. With the involvement of diverse V beta families in the secondary and tertiary responses, complementarity-determining region 3 length and clonotypic diversities within the V beta subfamilies gradually decreased throughout the response evolution. In tertiary repertoires, the usage of V beta 8.3 and focused clonal usage within each V beta subfamily were prominent. When noncognate separate CD4 help was provided during the induction of H60-specific secondary responses, extremely limited TCRs constituted the repertoire of reactive CD8 T cells, and most of these TCRs coincided with those observed in the secondary or tertiary repertoires provided with cognate help. CONCLUSIONS: This study is the first to characterize the diversity of TCRs specific for hematopoietic cell-specific mouse minor H antigens and demonstrate the effect of CD4 help on CD8 TCR repertoire diversity. Our data provide a basis for modeling therapeutic applications.
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