Structural requirements for antigen presentation by mouse CD1.
The structural basis for the T cell response to glycolipid antigens (Ags) remains poorly understood. T lymphocytes autoreactive for mouse CD1 (mCD1.1) or reactive for the glycosphingolipid alphagalactosylceramide (alpha-GalCer) presented by mCD1.1 have been described previously. In this paper it is shown that mutations at the top of the alpha helices and in the bottom of the Ag-binding groove can disrupt both mCD1.1 autoreactivity and alpha-GalCer recognition. The locations of the positions that affect T cell responses indicate that recognition of mCD1.1 is not likely to be unconventional or superantigen-like. Furthermore, the effects of the bottom of the pocket mutation suggest that the autoreactive response could require an autologous ligand, and they indicate that alpha-GalCer binds to the groove of mCD1.1, most likely with the shorter 18-carbon hydrophobic chain in the A' pocket. Natural killer T cell hybridomas with identical T cell antigen receptor (TCR) alpha chains and different beta chains respond differently to alpha-GalCer presented by mCD1.1 mutants. This finding indicates a role for TCR beta in defining natural killer T cell specificity, despite the more restricted diversity of the alpha chains in these cells. Overall, the data are consistent with a mode of lipoglycan recognition similar to that proposed for glycopeptides, in which the TCR alpha and beta chains survey a surface composed of both mCD1.1 and the carbohydrate portion of alpha-GalCer.
Burdin
N
N
La Jolla Institute of Allergy and Immunology, 10355 Science Center Drive, San Diego CA 92121, USA.
Brossay
L
L
Degano
M
M
Iijima
H
H
Gui
M
M
Wilson
I A
IA
Kronenberg
M
M
D019943:Amino Acid Substitution; D000818:Animals; D000941:Antigens / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D005699:Galactosylceramides / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000941:Antigens; D018949:Antigens, CD1; D005699:Galactosylceramides; D006028:Glycosphingolipids; D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011994:Recombinant Proteins