Early TCRalpha expression generates TCRalphagamma complexes that signal the DN-to-DP transition and impair development.
Clonotypic T cell receptor (TCR) genes undergo ordered rearrangement and expression in the thymus with the result that TCRalpha and TCRgamma proteins are not expressed in the same cell at the same time. Such "TCRalpha/gamma exclusion" is a feature of normal thymocyte differentiation, but it is abrogated in TCR-transgenic mice, which prematurely express transgenic TCRalpha proteins in early double-negative (DN) thymocytes. We report here that early expression of TCRalpha proteins results in the formation of TCRalphagamma complexes that efficiently signal the differentiation of DN into double-positive thymocytes independently of pre-TCR and TCRbeta expression. Thus, abrogation of TCRalpha/gamma exclusion by early TCRalpha expression results in the formation of isotypically mixed TCRalphagamma complexes whose in vivo signals circumvent TCRbeta selection and redirect thymocyte development along an aberrant developmental pathway.
Erman
Batu
B
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Feigenbaum
Lionel
L
Coligan
John E
JE
Singer
Alfred
A
D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
D046911:Macromolecular Substances; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta