McCormick D, Stauss H J, Thorpe C, Travers P, Dyson P J
Transplantation Biology Group, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, GB.
Eur J Immunol. 1996 Dec;26(12):2895-902. doi: 10.1002/eji.1830261214.
The P91A antigen was identified following mutation of P1 mastocytoma cells. The peptide epitope is encoded by a mutant form of the S3 subunit of the PA700 proteasome regulatory complex. P91A stimulates a strong CD8+ T cell response when expressed on tumor cells or normal tissue and P91A-specific T cells express a restricted range of T cell receptors. Although it is a strong Ld-binding peptide, P91A does not conform to the established motif for this major histocompatibility complex (MHC) molecule and this has hampered elucidation of the precise epitope. Ld predominantly associates with nonamer peptides; however, using a variety of complementary approaches, the P91A epitope is identified as the octamer QNHRALDL. In the absence of the Ld motif residue proline at position 2, residues 5-7 are primarily involved in MHC interaction. P91A is thus atypical in its interaction with Ld. Residues 1, 3, and 4 are found to influence T cell recognition of P91A. Definition of the P91A peptide will allow studies on P91A processing and interactions of the P91A peptide/MHC complex with T cell receptors of differing avidity to establish the basis for restricted T cell receptor usage. The basis for the failure of the P91A tum+ peptide (QNRRALDL) to bind to Ld is addressed by molecular modeling.
P91A抗原是在P1肥大细胞瘤细胞发生突变后被鉴定出来的。该肽表位由PA700蛋白酶体调节复合物S3亚基的突变形式编码。当在肿瘤细胞或正常组织上表达时，P91A能刺激强烈的CD8+ T细胞反应，且P91A特异性T细胞表达范围有限的T细胞受体。尽管P91A是一种与Ld结合能力很强的肽，但它不符合这种主要组织相容性复合体（MHC）分子已确定的基序，这阻碍了对精确表位的阐明。Ld主要与九聚体肽结合；然而，通过多种互补方法，P91A表位被鉴定为八聚体QNHRALDL。在第2位没有Ld基序残基脯氨酸的情况下，第5至7位残基主要参与MHC相互作用。因此，P91A与Ld的相互作用是非典型的。发现第1、3和4位残基会影响T细胞对P91A的识别。P91A肽的定义将有助于研究P91A的加工过程以及P91A肽/MHC复合物与不同亲和力的T细胞受体的相互作用，从而为限制T细胞受体的使用奠定基础。通过分子建模探讨了P91A tum+肽（QNRRALDL）不能与Ld结合的原因。
