title: Doubting the TCR coreceptor function of CD8alphaalpha.
abstract: "The beginning of wisdom is found in doubting; by doubting we come to question, and by seeking we may come upon the truth." -Pierre Abélard. CD8 is a glycoprotein expressed on hematopoietic cells. Two isoforms of CD8, CD8alphabeta and CD8alphaalpha, have been identified that are distinct in their expression and function. Whereas CD8alphabeta serves as a T cell receptor (TCR) coreceptor to enhance the functional avidity and is constitutively expressed on MHC class I-restricted T cells, CD8alphaalpha marks T cells that are distinct from the conventional thymus-selected and MHC-restricted CD4(+) or CD8alphabeta(+) T cells. Inconsistent with a coreceptor function, CD8alphaalpha decreases antigen sensitivity of the TCR, and it can be transiently or permanently expressed on T cells, regardless of the MHC restriction of the TCR or the presence of conventional coreceptors. Together, these observations indicate that CD8alphaalpha on T cells marks a differentiation stage and that it likely functions as a TCR corepressor to negatively regulate T cell activation.
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. hilde@liai.org
authors.forename: Hilde
authors.initials: H
authors.lastname: Cheroutre
authors.forename: Florence
authors.initials: F
authors.lastname: Lambolez
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C433839:CD8alphabeta antigen; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell