MHC-restricted T cell receptor signaling is required for alpha beta TCR replacement of the pre T cell receptor.
A developmental block is imposed on CD25(+)CD44(-) thymocytes at the beta-selection checkpoint in the absence of the pre T cell receptor (preTCR) alpha-chain, pTalpha. Early surface expression of a transgenic alphabeta TCR has been shown to partially circumvent this block, such that thymocytes progress to the CD4(+)CD8(+) double-positive stage. We wanted to analyze whether a restricting MHC element is required for alphabeta TCR-expressing double-negative (DN) thymocytes to overcome the developmental block in pTalpha-deficient animals. We used the HY-I knock-in model that endows thymocytes with alphabeta TCR expression in the DN compartment but has the advantage of physiological expression levels, in contrast to conventional TCR transgenes. On a pTalpha-deficient background, this HY-I TCR transgene 'rescued' CD25(+)CD44(-) thymocytes from apoptosis and enabled progression to later differentiation stages. On a non-selecting MHC background, however, pTalpha-deficient HY-I mice presented a pronounced reduction in numbers of splenocytes and thymocytes when compared to animals of selecting MHC genotype, showing that MHC restriction is necessary to drive HY-TCR-mediated rescue of pTalpha-deficient thymocytes.
Croxford
Andrew L
AL
Institute for Genetics, University of Cologne, Cologne, Germany.
Akilli-Ozturk
Ozlem
O
Rieux-Laucat
Frederic
F
Förster
Irmgard
I
Waisman
Ari
A
Buch
Thorsten
T
D000818:Animals; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D006182:H-Y Antigen; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha