Impaired NK1.1 T cell development in mice transgenic for a T cell receptor beta chain lacking the large, solvent-exposed cbeta FG loop.
A striking feature of the T cell receptor (TCR) beta chain structure is the large FG loop that protrudes freely into the solvent on the external face of the Cbeta domain. We have already shown that a transgene-encoded Vbeta8.2(+) TCR beta chain lacking the complete Cbeta FG loop supports normal development and function of conventional alpha/beta T cells. Thus, the FG loop is not absolutely necessary for TCR signaling. However, further analysis has revealed that a small population of alpha/beta T cells coexpressing NK1.1 are severely depleted in these transgenic mice. The few remaining NK1.1 T cells have a normal phenotype but express very low levels of TCR. We find that the TCR Vbeta8.2(+) chain lacking the Cbeta FG loop cannot pair efficiently with the invariant Valpha14-Jalpha281 TCR alpha chain commonly expressed by this T cell family. Consequently, fewer NK1.1 T cells develop in these mice. Our results suggest that expression of the Valpha14(+) TCR alpha chain is particularly sensitive to TCR-beta conformation. Development of NK1.1 T cells appears to need a TCR-beta conformation dependent on the presence of the Cbeta loop that is not necessarily required for assembly and function of TCRs on most alpha/beta T cells.
Degermann
S
S
Basel Institute for Immunology, CH-4005 Basel, Switzerland. degermann@bii.ch
Sollami
G
G
Karjalainen
K
K
D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D007694:Killer Cells, Natural / Q000378:metabolism*; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta