A CD8/Lck transgene is able to drive thymocyte differentiation

Ruben C Fragoso, Saiju Pyarajan, Hanna Yoko Irie, Steven J. Burakoff

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8α-associated Lck in driving CDS single positive (SP) thymocyte development We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8α fused to full-length Lck. In mice deficient for CD8α and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8α. A CD8α/Lck kinase-dead chimera also resulted in reconstitution of CDS SP thymocytes. Our results suggest that CD8α-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CDS SP development may not necessarily depend on Lck kinase activity.

Original languageEnglish (US)
Pages (from-to)6007-6017
Number of pages11
JournalJournal of Immunology
Volume177
Issue number9
StatePublished - Nov 1 2006
Externally publishedYes

Fingerprint

Thymocytes
Transgenes
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Fragoso, R. C., Pyarajan, S., Irie, H. Y., & Burakoff, S. J. (2006). A CD8/Lck transgene is able to drive thymocyte differentiation. Journal of Immunology, 177(9), 6007-6017.

A CD8/Lck transgene is able to drive thymocyte differentiation. / Fragoso, Ruben C; Pyarajan, Saiju; Irie, Hanna Yoko; Burakoff, Steven J.

In: Journal of Immunology, Vol. 177, No. 9, 01.11.2006, p. 6007-6017.

Research output: Contribution to journalArticle

Fragoso, RC, Pyarajan, S, Irie, HY & Burakoff, SJ 2006, 'A CD8/Lck transgene is able to drive thymocyte differentiation', Journal of Immunology, vol. 177, no. 9, pp. 6007-6017.
Fragoso RC, Pyarajan S, Irie HY, Burakoff SJ. A CD8/Lck transgene is able to drive thymocyte differentiation. Journal of Immunology. 2006 Nov 1;177(9):6007-6017.
Fragoso, Ruben C ; Pyarajan, Saiju ; Irie, Hanna Yoko ; Burakoff, Steven J. / A CD8/Lck transgene is able to drive thymocyte differentiation. In: Journal of Immunology. 2006 ; Vol. 177, No. 9. pp. 6007-6017.
@article{1b8487fd01e949b0a47750b2a85e3853,
title = "A CD8/Lck transgene is able to drive thymocyte differentiation",
abstract = "Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8α-associated Lck in driving CDS single positive (SP) thymocyte development We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8α fused to full-length Lck. In mice deficient for CD8α and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8α. A CD8α/Lck kinase-dead chimera also resulted in reconstitution of CDS SP thymocytes. Our results suggest that CD8α-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CDS SP development may not necessarily depend on Lck kinase activity.",
author = "Fragoso, {Ruben C} and Saiju Pyarajan and Irie, {Hanna Yoko} and Burakoff, {Steven J.}",
year = "2006",
month = "11",
day = "1",
language = "English (US)",
volume = "177",
pages = "6007--6017",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - A CD8/Lck transgene is able to drive thymocyte differentiation

AU - Fragoso, Ruben C

AU - Pyarajan, Saiju

AU - Irie, Hanna Yoko

AU - Burakoff, Steven J.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8α-associated Lck in driving CDS single positive (SP) thymocyte development We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8α fused to full-length Lck. In mice deficient for CD8α and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8α. A CD8α/Lck kinase-dead chimera also resulted in reconstitution of CDS SP thymocytes. Our results suggest that CD8α-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CDS SP development may not necessarily depend on Lck kinase activity.

AB - Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8α-associated Lck in driving CDS single positive (SP) thymocyte development We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8α fused to full-length Lck. In mice deficient for CD8α and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8α. A CD8α/Lck kinase-dead chimera also resulted in reconstitution of CDS SP thymocytes. Our results suggest that CD8α-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CDS SP development may not necessarily depend on Lck kinase activity.

UR - http://www.scopus.com/inward/record.url?scp=33750337551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750337551&partnerID=8YFLogxK

M3 - Article

C2 - 17056525

AN - SCOPUS:33750337551

VL - 177

SP - 6007

EP - 6017

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -