title: Lck availability during thymic selection determines the recognition specificity of the T cell repertoire.
abstract: Thymic selection requires signaling by the protein tyrosine kinase Lck to generate T cells expressing αβ T cell antigen receptors (TCR). For reasons not understood, the thymus selects only αβTCR that are restricted by major histocompatibility complex (MHC)-encoded determinants. Here, we report that Lck proteins that were coreceptor associated promoted thymic selection of conventionally MHC-restricted TCR, but Lck proteins that were coreceptor free promoted thymic selection of MHC-independent TCR. Transgenic TCR with MHC-independent specificity for CD155 utilized coreceptor-free Lck to signal thymic selection in the absence of MHC, unlike any transgenic TCR previously described. Thus, the thymus can select either MHC-restricted or MHC-independent αβTCR depending on whether Lck is coreceptor associated or coreceptor free. We conclude that the intracellular state of Lck determines the specificity of thymic selection and that Lck association with coreceptor proteins during thymic selection is the mechanism by which MHC restriction is imposed on a randomly generated αβTCR repertoire.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: François
authors.initials: F
authors.lastname: Van Laethem
authors.forename: Anastasia N
authors.initials: AN
authors.lastname: Tikhonova
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Pobezinsky
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tai
authors.forename: Motoko Y
authors.initials: MY
authors.lastname: Kimura
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Saout
authors.forename: Terry I
authors.initials: TI
authors.lastname: Guinter
authors.forename: Anthony
authors.initials: A
authors.lastname: Adams
authors.forename: Susan O
authors.initials: SO
authors.lastname: Sharrow
authors.forename: Günter
authors.initials: G
authors.lastname: Bernhardt
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
mesh_terms: D000818:Animals; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011991:Receptors, Virus; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D060168:Thymocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D011991:Receptors, Virus; C066100:poliovirus receptor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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