Heath W R, Vitiello A, Sherman L A
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
J Immunol. 1989 Sep 1;143(5):1441-6.
To identify epitopes recognized by alloreactive CTL we have examined H-2Kb-specific CTL for their recognition of synthetic peptides with sequences derived from the native Kb class I molecule. Consecutive nested peptides spanning the immunogenic alpha 1 and alpha 2 domains of Kb were tested for their capacity to inhibit CTL clones in their recognition of cells expressing the native Kb molecule. Inhibition by these peptides was found to be an extremely rare event. One peptide (Kb.111-122) did inhibit recognition by one particular CTL clone, clone 13. Upon further investigation it was observed that clone 13 also recognized peptide Kb.111-122 when presented in the context of the syngeneic MHC molecule, Kd. Considering that residues 111 to 122 are located at the base of the antigen groove, and clone 13 is able to recognize Kb.111-122 when presented by syngeneic target cells, we suggest that inhibition of this CTL clone may be due to MHC restricted, self-presentation of peptide rather than to direct binding of free peptide to the TCR. Taken together, these results suggest inhibition of allospecific CTL by MHC peptides is a rare event at least for Kb recognition. Furthermore, they demonstrate the need for caution when interpreting inhibition by peptide as evidence for recognition by the TCR of the corresponding region on the native molecule.
为了鉴定同种反应性CTL识别的表位，我们检测了H-2Kb特异性CTL对源自天然Kb I类分子序列的合成肽的识别。测试了跨越Kb免疫原性α1和α2结构域的连续嵌套肽抑制CTL克隆识别表达天然Kb分子细胞的能力。发现这些肽的抑制作用是极其罕见的事件。一种肽（Kb.111-122）确实抑制了一个特定CTL克隆（克隆13）的识别。进一步研究发现，当在同基因MHC分子Kd的背景下呈现时，克隆13也识别肽Kb.111-122。考虑到111至122位残基位于抗原槽底部，并且克隆13在同基因靶细胞呈现时能够识别Kb.111-122，我们认为该CTL克隆受到抑制可能是由于MHC限制的肽自身呈递，而不是游离肽与TCR的直接结合。综上所述，这些结果表明MHC肽对同种特异性CTL的抑制至少对于Kb识别来说是罕见事件。此外，它们证明在将肽的抑制作用解释为TCR识别天然分子上相应区域的证据时需要谨慎。
