A signaling role for the cytoplasmic segment of the CD8 alpha chain detected under limiting stimulatory conditions.
To test for the functional importance of the cytoplasmic segment of the CD8 molecule, a mouse T-cell hybridoma expressing a T-cell receptor specific for the class I major histocompatibility complex product H-2Kb was transfected with a set of CD8 alpha-chain (Ly-2) and/or beta-chain (Ly-3) genes encoding polypeptides with carboxyl-terminal truncations or substitutions. When challenged with Kb-positive splenocytes, transfectants expressing Ly-2 homodimers that lacked cytoplasmic tails responded nearly as effectively as wild-type Ly-2 transfectants. However in marked contrast to the wild-type Ly-2 transfectants, tailless Ly-2 transfectants were greatly impaired in their ability to respond to Kb-transfected L cells. Coexpression of the Ly-3 gene did not restore this impaired response. The unique functional property of the Ly-2 alpha cytoplasmic segment was further supported by the analysis of a chimeric Ly-3 subunit in which the cytoplasmic segment was replaced by the one from the Ly-2 alpha subunit. When associated with a soluble Ly-2 subunit lacking a transmembrane segment, the chimeric Ly-3 was indeed sufficient to restore the response to Kb-transfected L cells. Since the lateral mobility of the tailless Ly-2 molecules on the cell surface was nearly identical to that of the wild-type Ly-2 molecules, their partially impaired function may indicate that they have lost their cis-acting signaling properties but retained their ability to bind class I products of the major histocompatibility complex.
Letourneur
F
F
Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale, Marseille, France.
Gabert
J
J
Cosson
P
P
Blanc
D
D
Davoust
J
J
Malissen
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007376:Interleukin-2; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell