Receptor-specific allelic exclusion of TCRV alpha-chains during development
Standard
Receptor-specific allelic exclusion of TCRV alpha-chains during development. / Boyd, R; Kozieradzki, I; Chidgey, A; Mittrücker, H W; Bouchard, D; Timms, E; Kishihara, K; Ong, C J; Chui, D; Marth, J D; Mak, T W; Penninger, J M.
in: J IMMUNOL, Jahrgang 161, Nr. 4, 15.08.1998, S. 1718-27.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Receptor-specific allelic exclusion of TCRV alpha-chains during development
AU - Boyd, R
AU - Kozieradzki, I
AU - Chidgey, A
AU - Mittrücker, H W
AU - Bouchard, D
AU - Timms, E
AU - Kishihara, K
AU - Ong, C J
AU - Chui, D
AU - Marth, J D
AU - Mak, T W
AU - Penninger, J M
PY - 1998/8/15
Y1 - 1998/8/15
N2 - Expression of a single Ag receptor on lymphocytes is maintained via allelic exclusion that generates cells with a clonal receptor repertoire. We show in normal mice and mice expressing functionally rearranged TCR alphabeta transgenes that allelic exclusion at the TCR alpha locus is not operational in immature thymocytes, whereas most mature T cells express a single TCRV alpha-chain. TCRV alpha allelic exclusion in mature thymocytes is regulated through a CD45 tyrosine phosphatase-mediated signal during positive selection. Using functional and genetic systems for selection of immature double TCRV alpha+ thymocytes, we show that peptide-specific ligand recognition provides the signal for allelic exclusion, i.e., mature T cells maintain expression of the ligand-specific TCRV alpha-chain, but lose the nonfunctional receptor. Whereas activation of TCRV beta-chains or CD3epsilon leads to receptor internalization, TCRV alpha ligation promotes retention of the TCR on the cell surface. Although both TCRV alpha- and TCRV beta-chains trigger phosphotyrosine signaling, only the TCRV beta-chain mediates membrane recruitment of the GTPase dynamin. These data indicate that TCRV alpha-directed signals for positive selection control allelic exclusion in T cells, and that developmental signals can select for single receptor usage.
AB - Expression of a single Ag receptor on lymphocytes is maintained via allelic exclusion that generates cells with a clonal receptor repertoire. We show in normal mice and mice expressing functionally rearranged TCR alphabeta transgenes that allelic exclusion at the TCR alpha locus is not operational in immature thymocytes, whereas most mature T cells express a single TCRV alpha-chain. TCRV alpha allelic exclusion in mature thymocytes is regulated through a CD45 tyrosine phosphatase-mediated signal during positive selection. Using functional and genetic systems for selection of immature double TCRV alpha+ thymocytes, we show that peptide-specific ligand recognition provides the signal for allelic exclusion, i.e., mature T cells maintain expression of the ligand-specific TCRV alpha-chain, but lose the nonfunctional receptor. Whereas activation of TCRV beta-chains or CD3epsilon leads to receptor internalization, TCRV alpha ligation promotes retention of the TCR on the cell surface. Although both TCRV alpha- and TCRV beta-chains trigger phosphotyrosine signaling, only the TCRV beta-chain mediates membrane recruitment of the GTPase dynamin. These data indicate that TCRV alpha-directed signals for positive selection control allelic exclusion in T cells, and that developmental signals can select for single receptor usage.
KW - Alleles
KW - Animals
KW - Antigens, CD45
KW - Cell Differentiation
KW - Cell Membrane
KW - Dynamins
KW - GTP Phosphohydrolases
KW - Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
KW - Membrane Proteins
KW - Mice
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Microtubules
KW - Protein Tyrosine Phosphatases
KW - Receptors, Antigen, T-Cell, alpha-beta
KW - Signal Transduction
KW - T-Lymphocyte Subsets
KW - Transgenes
M3 - SCORING: Journal article
C2 - 9712036
VL - 161
SP - 1718
EP - 1727
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 4
ER -