title: Expression of a novel integrin beta 1 chain epitope and anti-beta 1 antibody-mediated enhancement of fibronectin binding are dependent on the stage of T cell differentiation.
abstract: Beta 1 integrins are a family of alpha beta heterodimers that serve as cell surface receptors for extracellular matrix proteins. We demonstrate that the anti-mouse integrin beta 1 chain mAb KMI6 selectively recognizes a beta 1 epitope that is constitutively expressed by certain immature thymocytes and is induced only slightly on mature thymocytes and peripheral T cells by activation with Con A. Because virtually all cells examined expressed beta 1 integrins on their surface, expression of the KMI6 epitope is T cell differentiation stage specific. Most CD3-4-8- thymocytes were KMI6+, with the lowest level of staining observed on the earliest CD44+IL-2R- cells within this subset. Expression was down-regulated during the CD3-4-8- to CD3-4-8+ transition, and lost by the CD4+8+ stage. Mature single positive thymocytes and resting peripheral T cells were also KMI6-. In contrast with the loss of the epitope before TCR expression by other thymocytes, most CD3+4-8- and certain CD8+ gamma delta TCR+ thymocytes were KMI6+ Addition of KMI6 to cell adhesion assays enhanced CD4-8- thymocyte, but not activated mature thymocyte or peripheral T cell, binding to fibronectin (via alpha 4 beta 1 and alpha 5 beta 1), whereas laminin binding (via alpha 6 beta 1) was unaffected. These properties distinguish the KMI6 epitope from other epitopes involved in beta 1 integrin activation in mice and other species. The unique selectivity of KMI6 recognition of beta 1 integrins, and its selective enhancement of ligand binding suggest that beta 1 integrin structure and factors that regulate beta 1 integrin binding are correlated with the stage of T cell differentiation.
authors.affiliation: Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: S A
authors.initials: SA
authors.lastname: Wadsworth
authors.forename: A C
authors.initials: AC
authors.lastname: Chang
authors.forename: M J
authors.initials: MJ
authors.lastname: Hong
authors.forename: M J
authors.initials: MJ
authors.lastname: Halvorson
authors.forename: S
authors.initials: S
authors.lastname: Otto
authors.forename: J E
authors.initials: JE
authors.lastname: Coligan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D003208:Concanavalin A / Q000494:pharmacology; D015536:Down-Regulation; D000939:Epitopes / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D002352:Carrier Proteins; D000939:Epitopes; D005353:Fibronectins; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D016023:Integrins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; D003208:Concanavalin A