Singer A, Kruisbeek A M, Andrysiak P M
J Immunol. 1984 May;132(5):2199-209.
The specificity of the T-accessory cell interactions that initiate primary allospecific cytotoxic T lymphocyte (CTL) responses were found to be surprisingly diverse and of three distinct major histocompatibility complex (MHC) specificities, involving responder T cell recognition of: a) self-Ia accessory cell determinants, b) allo-Ia accessory cell determinants, or c) allo-K/D accessory cell determinants. Any one of these T-accessory cell interactions was sufficient to initiate allospecific CTL responses. It was observed that when accessory cells did not express foreign class I MHC determinants, primary allospecific CTL responses were invariably initiated by Ia-restricted T-accessory cell interactions. In contrast, it was observed that when accessory cells did express foreign class I MHC determinants, primary allospecific CTL responses could be initiated by Ia-independent T-accessory cell interactions that were specific for allogeneic, but not self, K/D determinants and that did not involve recognition of polymorphic Ia determinants. The MHC specificities of the T-accessory cell interactions that initiate primary allospecific and primary trinitrophenyl (TNP)-self CTL responses were also compared. It was observed that primary allospecific and primary TNP-self CTL responses could be initiated by self-Ia-restricted T-accessory cell interactions, and that in both responses the Ia determinants that the responding T cells recognized as self-specificities on the accessory cell surface were those that their precursors had encountered on radiation-resistant thymic elements in their differentiation environment. In contrast to the initiation of primary TNP-self CTL responses that required the activation by accessory cells of Ia-restricted T helper (TH) cells, allospecific CTL responses could also be initiated by class I-restricted T cells specific for accessory cell K/D determinants. Interestingly, such class I-restricted T cells present in primary responder cell populations were triggered only by recognition of allogeneic, but not self, K/D accessory cell determinants, even when the accessory cells were modified with TNP. Thus, the present study demonstrates that primary allospecific CTL responses, but not TNP-self CTL responses, are initiated by Ia-restricted or Ia-independent cellular interaction pathways. These results raise the possibility that unprimed class I-restricted TH cells that mediate the Ia-independent cellular interaction pathway may predominantly express an allospecific, but not a self + X-specific, receptor repertoire. Possible mechanisms by which these distinct T-accessory cell interactions initiate primary allospecific CTL responses are discuss
引发初次同种异体特异性细胞毒性T淋巴细胞（CTL）反应的T辅助细胞相互作用的特异性出人意料地多样，具有三种不同的主要组织相容性复合体（MHC）特异性，涉及应答T细胞对以下物质的识别：a）自身Ia辅助细胞决定簇，b）同种异体Ia辅助细胞决定簇，或c）同种异体K/D辅助细胞决定簇。这些T辅助细胞相互作用中的任何一种都足以引发同种异体特异性CTL反应。据观察，当辅助细胞不表达外来的I类MHC决定簇时，初次同种异体特异性CTL反应总是由Ia限制的T辅助细胞相互作用引发。相反，据观察，当辅助细胞确实表达外来的I类MHC决定簇时，初次同种异体特异性CTL反应可以由Ia非依赖性T辅助细胞相互作用引发，这种相互作用对同种异体而非自身的K/D决定簇具有特异性，且不涉及对多态性Ia决定簇的识别。还比较了引发初次同种异体特异性和初次三硝基苯（TNP）-自身CTL反应的T辅助细胞相互作用的MHC特异性。据观察，初次同种异体特异性和初次TNP-自身CTL反应可以由自身Ia限制的T辅助细胞相互作用引发，并且在这两种反应中，应答T细胞在辅助细胞表面识别为自身特异性的Ia决定簇是其前体在分化环境中在抗辐射胸腺成分上遇到的那些决定簇。与需要辅助细胞激活Ia限制的T辅助（TH）细胞才能引发初次TNP-自身CTL反应不同，同种异体特异性CTL反应也可以由对辅助细胞K/D决定簇具有特异性的I类限制T细胞引发。有趣的是，即使辅助细胞用TNP修饰，初次应答细胞群体中存在的这种I类限制T细胞也仅通过识别同种异体而非自身的K/D辅助细胞决定簇而被触发。因此，本研究表明，初次同种异体特异性CTL反应而非TNP-自身CTL反应是由Ia限制或Ia非依赖性细胞相互作用途径引发的。这些结果增加了这样一种可能性，即介导Ia非依赖性细胞相互作用途径的未致敏I类限制TH细胞可能主要表达同种异体特异性而非自身+X特异性的受体库。讨论了这些不同的T辅助细胞相互作用引发初次同种异体特异性CTL反应的可能机制。
