Signaling efficiency of the T cell receptor controlled by a single amino acid in the beta chain constant region

被引:25
作者
Backstrom, BT [1 ]
Hausmann, BT [1 ]
Palmer, E [1 ]
机构
[1] BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND
关键词
D O I
10.1084/jem.186.11.1933
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A single amino acid residue, Gln(136), located within the connecting peptide domain of C beta controls the ability of the alpha/beta TCR to transmit a full signal. TCRs in which this CP residue is mutated to Phe, the residue found in TCR-gamma, are unresponsive to antigenic ligands. Interestingly, this C beta residue is either polar or charged in every species studied thus far, including the trout and the skate. In contrast, the analogous residue in C gamma is always hydrophobic. In spite of their compromised antigen responsiveness, the mutant TCR complex contains the CD3-gamma, -delta, -epsilon, and -zeta; chains, and undergoes zeta chain phosphorylation and ZAP-70 recruitment. However, the biological response of the mutant TCR could be rescued with a calcium ionophore, implying that mutant TCRs are defective in generating a calcium-mediated signal. The implications of the differences between C beta and C gamma are considered.
引用
收藏
页码:1933 / 1938
页数:6
相关论文
共 27 条
  • [1] GENETIC AND MUTATIONAL ANALYSIS OF THE T-CELL ANTIGEN RECEPTOR
    ASHWELL, JD
    KLAUSNER, RD
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1990, 8 : 139 - 167
  • [2] Backstrom BT, 1997, EUR J IMMUNOL, V27, P1433
  • [3] A motif within the T cell receptor alpha chain constant region connecting peptide domain controls antigen responsiveness
    Backstrom, BT
    Milia, E
    Peter, A
    Jaureguiberry, B
    Baldari, CT
    Palmer, E
    [J]. IMMUNITY, 1996, 5 (05) : 437 - 447
  • [4] BIGBY M, 1993, J IMMUNOL, V151, P4465
  • [5] Campbell K S, 1994, Semin Immunol, V6, P393, DOI 10.1006/smim.1994.1049
  • [6] THE ZETA-CHAIN IS ASSOCIATED WITH A TYROSINE KINASE AND UPON T-CELL ANTIGEN RECEPTOR STIMULATION ASSOCIATES WITH ZAP-70, A 70-KDA TYROSINE PHOSPHOPROTEIN
    CHAN, AC
    IRVING, BA
    FRASER, JD
    WEISS, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (20) : 9166 - 9170
  • [7] MOST GAMMA-DELTA-T-CELLS DEVELOP NORMALLY IN BETA-2-MICROGLOBULIN-DEFICIENT MICE
    CORREA, I
    BIX, M
    LIAO, NS
    ZIJLSTRA, M
    JAENISCH, R
    RAULET, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (02) : 653 - 657
  • [8] CD3 delta deficiency arrests development of the alpha beta but not the gamma delta T cell lineage
    Dave, VP
    Cao, ZS
    Browne, C
    Alarcon, B
    FernandezMiguel, G
    Lafaille, J
    delaHera, A
    Tonegawa, S
    Kappes, DJ
    [J]. EMBO JOURNAL, 1997, 16 (06) : 1360 - 1370
  • [9] AN ANALYSIS OF SEQUENCE VARIATION IN THE BETA-CHAIN FRAMEWORK AND COMPLEMENTARITY-DETERMINING REGIONS OF AN ALLOREACTIVE T-CELL RECEPTOR
    DIGIUSTO, DL
    PALMER, E
    [J]. MOLECULAR IMMUNOLOGY, 1994, 31 (09) : 693 - 699
  • [10] Structure of the complex between human T-cell receptor, viral peptide and HLA-A2
    Garboczi, DN
    Ghosh, P
    Utz, U
    Fan, QR
    Biddison, WE
    Wiley, DC
    [J]. NATURE, 1996, 384 (6605) : 134 - 141