Maintenance of TCR clonality in T cells expressing genes for two TCR heterodimers

doi:10.1073/pnas.121179998

Maintenance of TCR clonality in T cells expressing genes for two TCR heterodimers

^*Immunology Program, Memorial Sloan-Kettering Cancer Center, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021; and ^‡Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520

Contributed by Charles A. Janeway, Jr.

Abstract

T cell receptor (TCR) allelic exclusion is believed to be primarily mediated by suppression of further recombination at the TCR locus after the expression of a functional TCR protein. Genetic allelic exclusion has been shown to be leaky for the β chain and, more commonly, for the α chain. Here, we demonstrate an additional mechanism by which T cells can maintain monoclonality. T cells from double TCR transgenic mice express only one or the other of the two available TCRs at the cell surface. This “functional allelic exclusion” is apparently due to control of the TCR assembly process because these T cells express RNA and protein for all four transgenic TCR proteins. Lack of cell surface expression of the second TCR may be controlled by a failure to assemble the TCR heterodimer.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: d-sant'angelo{at}ski.mskcc.org.
Abbreviations:

TCR,

T cell receptor;

FACS,

fluorescence-activated cell sorter;

AND,

TCR transgenic mouse;

MBP,

myelin basic protein;

RT,

reverse transcription;

MCC,

moth cytochrome c peptide;

CA,

chicken conalbumin;

wt,

wild type