title: [Expression anomalies of the CD3-TCR complex expression and immunodeficiencies].
abstract: Molecular characterization of immunodeficiencies contributes to a better understanding of the physiological mechanisms of immune function. The T cell receptor is a heterodimer (alpha/beta or gamma/delta) associated with four transmembrane units of the CD3 complex (gamma, delta, epsilon and zeta). We herein summarize the immunodeficiency states resulting from defects in genes encoding the CD3 complex. Such analysis highlights the respective role of each of these chains in T lymphocyte development and underscores differences between T lymphocyte development in man and mouse. Currently, there is a growing body of knowledge on immunodeficiencies specifically involving the four chains of the CD3, namely gamma, delta, epsilon and zeta. Thus, we can compare the phenotypes observed in these patients with those seen in mice knockout for these genes. The main differences observed involve the respective roles of the CD3gamma chain as well as the CD3delta, whose functions seem to be reciprocal between the two species. Indeed, in the mouse, knockout of CD3delta allows some degree of T lymphocyte differentiation since mature CD4 and CD8 as well as TCRgammadelta T lymphocytes are observed in the periphery. In contrast, deleterious mutation of the CD3delta encoding gene in the human leads to a severe combined immunodeficiency characterised by the complete absence of mature T cell subpopulations including TCRalpha/beta and TCRgamma/delta. Reciprocally, in the human, mutation of the CD3gamma encoding gene leads to a moderate immunodeficiency which contrasts with the complete block of T cell differentiation observed in mice knockout for this gene. This article brings into focus the knowledge gained through studies of immunodeficiency mouse models with the pathophysiological state observed in human disease.
authors.affiliation: Département de microbiologie et d'immunologie, Université de Montréal, CHU Sainte-Justine, 3175, chemin de la Côte Sainte-Catherine, Montréal (Québec), H3T 1C5 Canada. Francoise.le.deist@umontreal.ca
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint Basile
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
authors.forename: Claire
authors.initials: C
authors.lastname: Hivroz
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D002648:Child; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018448:Models, Immunological; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000002:abnormalities; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; C121704:CD3 antigen, zeta chain; C472562:CD3delta antigen; D047908:Intracellular Signaling Peptides and Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases