TCR diversity of H60-specific CD8 T cells during the response evolution and influence of CD4 help

Abstract

BACKGROUNDS.: 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 Vβ 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 Vβ families in the secondary and tertiary responses, complementarity-determining region 3 length and clonotypic diversities within the Vβ subfamilies gradually decreased throughout the response evolution. In tertiary repertoires, the usage of Vβ8.3 and focused clonal usage within each Vβ 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. © 2009 by Lippincott Williams & Wilkins.