Human CD8 beta, but not mouse CD8 beta, can be expressed in the absence of CD8 alpha as a beta beta homodimer.
The T cell coreceptor CD8 exists on mature T cells as disulfide-linked homodimers of CD8 alpha polypeptide chains and heterodimers of CD8 alpha- and CD8 beta-chains. The function of the CD8 alpha-chain for binding to MHC class I and associating with the tyrosine kinase p56lck was demonstrated with CD8 alpha alpha homodimers. CD8 alpha beta functions as a better coreceptor, but the actual function of CD8 beta is less clear. Addressing this issue has been hampered by the apparent inability of CD8 beta to be expressed without CD8 alpha. This study demonstrates that human, but not mouse, CD8 beta can be expressed on the cell surface without CD8 alpha in both transfected COS-7 cells and murine lymphocytes. By creating chimeric proteins, we show that the murine Ig domain of CD8 beta is responsible for the lack of expression of murine CD8 beta beta dimers. In contrast to CD8 alpha alpha, CD8 beta beta is unable to bind MHC class I in a cell-cell adhesion assay. Detection of this form of CD8 should facilitate studies on the function of the CD8 beta-chain and indicates that caution should be used when interpreting studies on CD8 function using chimeric protein with the murine CD8 beta beta Ig domain. In addition, we demonstrate that the Ig domains of CD8 alpha are also involved in controlling the ability of CD8 to be expressed. Mutation of B- and F-strand cysteine residues in CD8 alpha reduced the ability of the protein to fold properly and, therefore, to be expressed.
Devine
L
L
Department of Laboratory Medicine, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Kieffer
L J
LJ
Aitken
V
V
Kavathas
P B
PB
D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D013045:Species Specificity; D014162:Transfection
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D020033:Protein Isoforms; D003545:Cysteine