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

Jung Hwa Choi, Su Jeong Ryu, Kyung Min Jung, Sol Kim, Jun Chang, Tae Woo Kim, Eun Young Choi

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1609-1616
Number of pages8
JournalTransplantation
Volume87
Issue number11
DOIs
Publication statusPublished - 2009 Jun 15

Fingerprint

T-Cell Antigen Receptor
Complementarity Determining Regions
T-Lymphocytes
Minor Histocompatibility Antigens
Bone Marrow Transplantation
Leukemia
Therapeutics

Keywords

  • CD4 help
  • CD8 T-cell response
  • Minor histocompatibility antigen H60
  • TCR repertoire diversity

ASJC Scopus subject areas

  • Transplantation

Cite this

TCR diversity of H60-specific CD8 T cells during the response evolution and influence of CD4 help. / Choi, Jung Hwa; Ryu, Su Jeong; Jung, Kyung Min; Kim, Sol; Chang, Jun; Kim, Tae Woo; Choi, Eun Young.

In: Transplantation, Vol. 87, No. 11, 15.06.2009, p. 1609-1616.

Research output: Contribution to journalArticle

Choi, Jung Hwa ; Ryu, Su Jeong ; Jung, Kyung Min ; Kim, Sol ; Chang, Jun ; Kim, Tae Woo ; Choi, Eun Young. / TCR diversity of H60-specific CD8 T cells during the response evolution and influence of CD4 help. In: Transplantation. 2009 ; Vol. 87, No. 11. pp. 1609-1616.
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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.",
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AU - Choi, Jung Hwa

AU - Ryu, Su Jeong

AU - Jung, Kyung Min

AU - Kim, Sol

AU - Chang, Jun

AU - Kim, Tae Woo

AU - Choi, Eun Young

PY - 2009/6/15

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N2 - 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.

AB - 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.

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KW - CD8 T-cell response

KW - Minor histocompatibility antigen H60

KW - TCR repertoire diversity

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