TCR diversity of H60-specific CD8 T cells during the response evolution and influence of CD4 help.
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.
Choi
Jung Hwa
JH
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Ryu
Su Jeong
SJ
Jung
Kyung Min
KM
Kim
Sol
S
Chang
Jun
J
Kim
Tae Woo
TW
Choi
Eun Young
EY
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000637:transplantation
D015704:CD4 Antigens; D016827:CD8 Antigens; D017931:DNA Primers; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta