CLONE-SPECIFIC T-CELL RECEPTOR ANTAGONISTS OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I RESTRICTED CYTOTOXIC T-CELLS

被引:261
作者
JAMESON, SC
CARBONE, FR
BEVAN, MJ
机构
[1] UNIV WASHINGTON,HOWARD HUGHES MED INST,DEPT IMMUNOL,SL-15,SEATTLE,WA 98195
[2] MONASH UNIV SCH MED,DEPT PATHOL & IMMUNOL,PRAHRAN,VIC 3181,AUSTRALIA
关键词
D O I
10.1084/jem.177.6.1541
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 previous report showed that the proliferative response of helper T cells to class II major histocompatibility complex (MHC)-restricted antigens can be inhibited by analogues of the antigen, which act as T cell receptor (TCR) antagonists. Here we define and analyze peptide variants that antagonize various functions of class I MHC-restricted cytotoxic T lymphocyte (CTL) clones. Of 64 variants at individual TCR contact sites of the K(b)-restricted octamer peptide ovalbumin257-264 (OVAp), a very high proportion (40%) antagonized lysis by three OVAp-specific CTL clones. This effect was highly clone specific, since many antagonists for one T cell done have differential effects on another. We show that this inhibition of CTL function is not a result of T cell-T cell interaction, precluding veto-like phenomena as a mechanism for antagonism. Moreover, we present evidence for direct interaction between the TCR and antagonist-MHC complexes. In further analysis of the T cell response, we found that serine esterase release and cytokine production are susceptible to TCR antagonism similarly to lysis. Ca2+ flux, an early event in signaling, is also inhibited by antagonists but may be more resistant to the antagonist effect than downstream responses.
引用
收藏
页码:1541 / 1550
页数:10
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