Moore Tamson V, Lyons Gretchen E, Brasic Natasha, Roszkowski Jeffrey J, Voelkl Simon, Mackensen Andreas, Kast W Martin, Le Poole I Caroline, Nishimura Michael I
Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
Cancer Immunol Immunother. 2009 May;58(5):719-28. doi: 10.1007/s00262-008-0594-2. Epub 2008 Oct 3.
Effective immunotherapy using T cell receptor (TCR) gene-modified T cells requires an understanding of the relationship between TCR affinity and functional avidity of T cells. In this study, we evaluate the relative affinity of two TCRs isolated from HLA-A2-restricted, gp100-reactive T cell clones with extremely high functional avidity. Furthermore, one of these T cell clones, was CD4- CD8- indicating that antigen recognition by this clone was CD8 independent. However, when these TCRs were expressed in CD8- Jurkat cells, the resulting Jurkat cells recognized gp100:209-217 peptide loaded T2 cells and had high functional avidity, but could not recognize HLA-A2+ melanoma cells expressing gp100. Tumor cell recognition by Jurkat cells expressing these TCRs could not be induced by exogenously loading the tumor cells with the native gp100:209-217 peptide. These results indicate that functional avidity of a T cell does not necessarily correlate with TCR affinity and CD8-independent antigen recognition by a T cell does not always mean its TCR will transfer CD8-independence to other effector cells. The implications of these findings are that T cells can modulate their functional avidity independent of the affinity of their TCRs.
使用经T细胞受体（TCR）基因修饰的T细胞进行有效的免疫治疗需要了解T细胞的TCR亲和力与功能亲合力之间的关系。在本研究中，我们评估了从具有极高功能亲合力的HLA-A2限制性、gp100反应性T细胞克隆中分离出的两种TCR的相对亲和力。此外，这些T细胞克隆之一为CD4-CD8-，表明该克隆的抗原识别不依赖CD8。然而，当这些TCR在CD8-Jurkat细胞中表达时，产生的Jurkat细胞能够识别负载gp100:209-217肽的T2细胞，并且具有高功能亲合力，但无法识别表达gp100的HLA-A2+黑色素瘤细胞。用天然gp100:209-217肽对外源负载肿瘤细胞，并不能诱导表达这些TCR的Jurkat细胞识别肿瘤细胞。这些结果表明，T细胞的功能亲合力不一定与TCR亲和力相关，并且T细胞的CD8非依赖性抗原识别并不总是意味着其TCR会将CD8非依赖性传递给其他效应细胞。这些发现的意义在于，T细胞可以独立于其TCR的亲和力来调节其功能亲合力。
