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Selective inhibition of interleukin 2 gene function following thymocyte antigen/major histocompatibility complex receptor crosslinking: possible thymic selection mechanism

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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Considerable evidence now exists to support the notion that the 50-kDa sheep erythrocyte binding protein, T11, represents an essential cell surface component of a human T-cell-linkage activation pathway. Furthermore, it is known that the human T-cell antigen-major histocompatibility complex (MHC) receptor complex T3-Ti is capable of regulating cell growth mediated by the T11 structure. Here the authors show that, within the T3/sup +/ thymocyte compartment, T3-Ti crosslinking rapidly inhibits T11-initiated interleukin 2 (IL-2) gene transcription and translation. This inhibition is restricted to the IL-2 gene (IL2) as transcription of both the IL-2 receptor gene (IL2R) and the Ti-..beta..-chain gene (TCRB) are not affected (human gene designations are in parentheses). Perhaps more importantly, T3-Ti-mediated IL-2 inhibition of this type is not operational in peripheral T lymphocytes. The results imply that the majority of T3/sup +/ thymocytes are functionally distinct from peripheral T lymphocytes despite their T3/sup +/ phenotype and may possess a unique endogenous regulatory component for suppressing IL-2 gene activity. Moreover, since IL-2 is likely rate-limiting for growth within the thymus, the findings provide one plausible mechanism for thymic selection-namely, T3-Ti crosslinking of thymocytes upon interaction with self-major histocompatibility complex inhibits clonal expansion of high-affinity autoreactive cells.
Research Organization:
Harvard Medical School, Boston, MA (USA)
OSTI ID:
6468518
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:23; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIGENS
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL PROLIFERATION
CHEMICAL ACTIVATION
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
CROSS-LINKING
GENE REGULATION
GENES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYBRIDIZATION
IMMUNOLOGY
LABELLED COMPOUNDS
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MITOGENS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
POLYMERIZATION
PRIMATES
PROTEINS
PYRIMIDINES
RECEPTORS
RIBOSIDES
SOMATIC CELLS
THYMIDINE
THYMOCYTES
TRANSCRIPTION
TRITIUM COMPOUNDS
VERTEBRATES