TCR beta chain influences but does not solely control autoreactivity of V alpha 14J281T cells.
CD1d-dependent accumulation of alphabeta T cells bearing a canonical Valpha14Jalpha281 alpha-chain (Valpha14+ T cells) is thought to model positive selection of lipid-specific T cells, based on their ability to recognize CD1d-presented self glycolipid(s). However, it has been difficult to demonstrate self ligand specificity in this system, as most Valpha14+ T cells do not exhibit significant autoreactivity despite high reactivity to alpha-galactosylceramide presented by CD1d (alpha-GalCer/CD1d). To assess the role of TCRbeta chain in determining the alpha-GalCer/CD1d vs autoreactive specificity of Valpha14+ T cells, we conducted TCRalpha or TCRbeta chain transduction experiments. In this study we demonstrate, by combining different TCRbeta chains with the Valpha14 alpha-chain in retrovirally transduced T cell lines, that the Valpha14 alpha-chain plays a primary role, necessary but not sufficient for imparting alpha-GalCer/CD1d recognition. beta-Chain usage alone is not the sole factor that controls the extent of autoreactivity in Valpha14+ T cells, since transduction of TCRalphabeta chains from a high CD1d autoreactive Valpha14+ T cell line conferred the alpha-GalCer/CD1d specificity without induction of autoreactivity. Thus, heterogeneity of Valpha14+ T cell reactivity is due to both beta-chain diversity and control mechanism(s) beyond primary TCR structure.
Gui
M
M
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Li
J
J
Wen
L J
LJ
Hardy
R R
RR
Hayakawa
K
K
D000595:Amino Acid Sequence; D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D005699:Galactosylceramides / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D018949:Antigens, CD1; D055610:Antigens, CD1d; D001324:Autoantigens; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta