Alloreactive CD8+ T cells can recognize unusual, rare, and unique processed peptide/MHC complexes.
Alloreactive CD8+ T cells can recognize unusual, rare, and unique processed peptide/MHC complexes.
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同种异体反应性 CD8 T 细胞可以识别不寻常、稀有和独特的加工肽/MHC 复合物。
作者：
S. Malarkannan;F. Gonzalez;V. Nguyen;G. Adair;N. Shastri
作为同种异体反应性T细胞配体的自身肽/MHC I类复合物的身份和丰度在很大程度上仍然未知。以Kb限制性同种异体反应性T细胞为探针，通过表达克隆分离出Ag前体基因--腺苷磷酸核糖转移酶（APRT）。其天然加工产物被鉴定为SLVELTSL（SEL 8）八肽。SEL 8肽与先前鉴定的刺激相同T细胞的SVVEFSSL（JAL 8）肽共有5个残基，但在主要p5锚位置缺少关键的苯丙氨酸/酪氨酸残基。尽管缺乏这个关键的保守锚残基，但SEL 8被Kb MHC紧密结合，并且以低于10个拷贝/细胞表达。APC中供体APRT基因的突变导致APC刺激T细胞的能力同时丧失。结果证实，肽/MHC复合物在细胞中的展示超过了基于共识基序的预测，并且CD 8+同种异体反应性和常规Ag特异性T细胞在识别独特和罕见的肽/MHC I类复合物的能力方面是不可区分的。
The identity and abundance of self-peptide/MHC class I complexes that serve as ligands for alloreactive T cells remain largely unknown. Using the Kb-restricted, alloreactive T cells as a probe, the Ag precursor gene, adenosine phosphoribosyl transferase (APRT), was isolated by expression cloning. Its naturally processed product was identified as the SLVELTSL (SEL8) octapeptide. The SEL8 peptide shared five residues with the previously identified SVVEFSSL (JAL8) peptide that stimulated the same T cell, but lacked the critical phenylalanine/tyrosine residue at the primary p5 anchor position. Despite the absence of this key conserved anchor residue, SEL8 was bound tightly by Kb MHC and yet was expressed at less than 10 copies/cell. Mutations in the donor APRT gene in the APC caused a concomitant loss in the ability of APCs to stimulate T cells. The results confirm that the display of peptide/MHC complexes in cells exceeds the predictions based upon consensus motifs, and that CD8+ alloreactive and conventional Ag-specific T cells are indistinguishable in their ability to recognize unique and rare peptide/MHC class I complexes.