An essential role for the stalk region of CD8 beta in the coreceptor function of CD8.
The CD8alphabeta heterodimer is integral to the selection of the class I-restricted lineage in the thymus; however, the contribution of the CD8beta chain to coreceptor function is poorly understood. To understand whether the CD8beta membrane proximal stalk region played a role in coreceptor function, we substituted it with the corresponding sequence from the CD8alpha polypeptide and expressed the hybrid molecule in transgenic mice in place of endogenous CD8beta. Although the stalk-swapped CD8beta was expressed on the cell surface as a disulfide-bonded heterodimer at equivalent levels of expression to an endogenous CD8beta molecule, it failed to restore selection of CD8(+) class I MHC-restricted T cells and it altered the response of peripheral T cells. Thus, the stalk region of the CD8beta polypeptide has an essential role in ensuring functionality of the CD8alphabeta heterodimer and its replacement compromises the interaction of CD8 with peptide-MHC complexes.
Rettig
Lorna
L
Molecular Immunology, Medical Research Council National Institute for Medical Research, London, United Kingdom.
McNeill
Louise
L
Sarner
Nitza
N
Guillaume
Philippe
P
Luescher
Immanuel
I
Tolaini
Mauro
M
Kioussis
Dimitris
D
Zamoyska
Rose
R
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D019281:Dimerization; D017353:Gene Deletion; D050939:Gene Fusion / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000502:physiology*; D019076:Transgenes / Q000276:immunology
D016827:CD8 Antigens; C431698:CD8alpha antigen; C433839:CD8alphabeta antigen; C477867:CD8beta antigen; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta