title: Influence of human CD8 on antigen recognition by T-cell receptor-transduced cells.
abstract: The CD8 coreceptor on T cells has two functions. Namely, CD8 acts to stabilize the binding of the T-cell receptor (TCR) to the peptide-MHC complex while localizing p56(lck) (lck) to the TCR/CD3 complex to facilitate early signaling events. Although both functions may be critical for efficient activation of a CTL, little is known about how the structural versus signaling roles of CD8, together with the relative strength of the TCR, influences T-cell function. We have addressed these issues by introducing full-length and truncated versions of the CD8alpha and CD8beta chains into CD8(-) Jurkat cell clones expressing cloned TCRs with known antigen specificity and relative affinities. Using a combination of antigen recognition and tetramer-binding assays, we find that the intracellular lck-binding domain of CD8 is critical for enhanced T-cell activation regardless of the relative strength of the TCR. In contrast, the extracellular domain of CD8 seems to be critical for TCRs with lower affinity but not those with higher affinity. Based on our results, we conclude that there are different requirements for CD8 to enhance T-cell function depending on the strength of its TCR.
authors.affiliation: Department of Surgery, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Gretchen E
authors.initials: GE
authors.lastname: Lyons
authors.forename: Tamson
authors.initials: T
authors.lastname: Moore
authors.forename: Natasha
authors.initials: N
authors.lastname: Brasic
authors.forename: Mingli
authors.initials: M
authors.lastname: Li
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Roszkowski
authors.forename: Michael I
authors.initials: MI
authors.lastname: Nishimura
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D017252:CD3 Complex; D016827:CD8 Antigens; C431698:CD8alpha antigen; C433839:CD8alphabeta antigen; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)