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Originally published In Press as doi:10.1074/jbc.M209591200 on December 8, 2002

J. Biol. Chem., Vol. 278, Issue 10, 8564-8571, March 7, 2003
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The Accessory Molecules CD5 and CD6 Associate on the Membrane of Lymphoid T Cells*

Idoia GimferrerDagger §, Montse FarnósDagger , Maria Calvo||**, María MittelbrunnDagger Dagger , Carlos Enrich§§, Francisco Sánchez-MadridDagger Dagger , Jordi VivesDagger , and Francisco LozanoDagger ¶¶

From the Dagger  Servei d'Immunologia, Institut Clínic d'Infeccions i Immunologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona 08036, || Institut d'Investigacions Biomèdiques August Pi i Sunyer-Serveis Cientifico-Tècnics, Facultat de Medicina, Universitat de Barcelona, Barcelona 08036, §§ Departament de Biologia Cellular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona 08036, and Dagger Dagger  Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain

CD5 and CD6 are closely related lymphocyte surface receptors of the scavenger receptor cysteine-rich superfamily, which show highly homologous extracellular regions but little conserved cytoplasmic tails. Both molecules are expressed on the same lymphocyte populations (thymocytes, mature T cells, and B1a cells) and share similar co-stimulatory properties on mature T cells. Although several works have been reported on the molecular associations and the signaling pathway mediated by CD5, very limited information is available for CD6 in this regard. Here we show the physical association of CD5 and CD6 at the cell membrane of lymphocytes, as well as their localization at the immunological synapse. CD5 and CD6 co-immunoprecipitate from Brij 96 but not Nonidet P-40 cell lysates, independently of both the co-expression of other lymphocyte surface receptors and the integrity of CD5 cytoplasmic region. Fluorescence resonance energy transfer analysis, co-capping, and co-modulation experiments demonstrate the physical in vivo association of CD5 and CD6. Analysis of T cell/antigen-presenting cells conjugates shows the accumulation of both molecules at the immunological synapse. These results indicate that CD5 and CD6 are structurally and physically related receptors, which may be functionally linked to provide either similar or complementary accessory signals during T cell activation and/or differentiation.

* This work was supported in part by Ministerio de Ciencia y Tecnología Grant SAF 2001-1832 and Comissió Interdepartamental de Reserca i Innovació Tecnològica Grant 2001SGR 00388.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of Premio Fin de Residencia Emili Letang fellowship from the Hospital Clínic.

Recipient of fellowship from Institut d'Investigacions Biomèdiques August Pi i Sunyer.

** Recipient of fellowship from FIS-Institut d'Investigacions Biomèdiques August Pi i Sunyer.

¶¶ To whom correspondence should be addressed: Servei d'Immunologia, Hospital Clínic i Provincial de Barcelona, Villarroel 170, Barcelona 08036, Spain. Tel.: 34-93-4544920; Fax: 34-93-4518038; E-mail: lozano@medicina.ub.es.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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