Tumors are immunogenic and the non-synonymous point mutations harbored by tumors are a source of their immunogenicity. Immunologists have long been enamored by the idea of synthetic peptides corresponding to mutated epitopes (neoepitopes) as specific “vaccines” against tumors presenting those neoepitopes in context of MHC I. Tumors may harbor hundreds of point mutations and it would require effective prediction algorithms to identify candidate neoepitopes capable of eliciting potent tumor-specific CD8⁺ T cell responses. Our current understanding of MHC I-restricted epitopes come from the observance of CD8⁺ T cell responses against viral (vaccinia, lymphocytic choriomeningitis etc.) and model (chicken ovalbumin, hen egg lysozyme etc.) antigens. Measurable CD8⁺ T cell responses elicited by model or viral antigens are always directed against epitopes possessing strong binding affinity for the restricting MHC I alleles. Immense collective effort to develop methodologies combining genomic sequencing, bioinformatics and traditional immunological techniques to identify neoepitopes with strong binding affinity to MHC I has only yielded inaccurate prediction algorithms. Additionally, new evidence has emerged suggesting that neoepitopes, which unlike the epitopes of viral or model antigens have closely resembling wild-type counterparts, may not necessarily demonstrate strong affinity to MHC I. Our bearing need recalibration.

肿瘤是免疫原性的，肿瘤具有的非同义点突变是其免疫原性的来源。长期以来，免疫学家一直迷恋与突变表位（新表位）相对应的合成肽，作为针对在MHC I背景下呈现那些新表位的肿瘤的特异性“疫苗”。肿瘤可能具有数百个点突变，因此需要有效的预测算法来鉴定能够引发有效的肿瘤特异性CD8 ⁺ T细胞反应的候选新表位。我们目前对MHC I限制性表位的了解来自对病毒（牛痘，淋巴细胞性脉络膜炎等）和模型（鸡卵白蛋白，鸡蛋溶菌酶等）抗原的CD8 ⁺ T细胞反应的观察。可测量的CD8 ⁺由模型或病毒抗原引起的T细胞反应总是针对对限制性MHC I等位基因具有强大结合亲和力的表位。致力于开发将基因组测序，生物信息学和传统免疫学技术相结合的方法的巨大集体努力，以鉴定对MHC I具有强结合亲和力的新表位仅产生了不准确的预测算法。此外，新的证据表明，与病毒或模型抗原的抗原决定簇具有非常相似的野生型对应物的新表位可能不一定显示出对MHC I的强亲和力。我们的轴承需要重新校准。