Requirement of CD3 complex-associated signaling functions for expression of rearranged T cell receptor beta VDJ genes in early thymic development.
During alpha beta thymocyte development, the clonotypic alpha beta-T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR-CD3 complex: the pre-TCR, containing a clonotypic TCR-beta chain and invariant pre-Talpha, is expressed on pre-T cells before rearrangement of the TCR-alpha locus. Moreover, clonotype-independent CD3 complexes (CIC) appear on pro-T cells before VDJ rearrangements of TCR-beta genes. The pre-TCR is known to mediate TCR-beta selection, the prerequisite for maturation of CD4(-)8(-) double negative (DN) thymocytes to the CD4(+)8(+) double positive stage. A developmental function of CIC has so far not been delineated. In mice single deficient and double deficient for CD3zeta/eta and/or p56(lck), we observe a pronounced reduction in the proportions of CD25(+) DN thymocytes that express intracellular TCR-beta chains. TCR-beta transcripts are reduced in parallel with TCR-beta polypeptide chains whereas no reduction in TCR-beta locus rearrangements could be detected. Wild-type levels of TCR-beta transcripts and of cells expressing TCR-beta polypeptide chains are induced by treatment with anti-CD3epsilon mAb. The data suggest that the initial expression of rearranged TCR-beta VDJ genes in pro-T cell to pre-T cell progression is dependent on CD3 complex signaling, and thus define a putative developmental function for CIC.
Würch
A
A
Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany.
Biro
J
J
Potocnik
A J
AJ
Falk
I
I
Mossmann
H
H
Eichmann
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D017931:DNA Primers; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)