Thomas D B, Hodgson J, Riska P F, Graham C M
National Institute for Medical Research, Mill Hill, London, U.K.
J Immunol. 1990 Apr 1;144(7):2789-94.
Evidence is presented for an endogenous route of Ag processing for CD4+ T cell recognition of influenza hemagglutinin that requires obligatory traffic of de novo synthesized hemagglutinin across the lumen of the endoplasmic reticulum for processing in a cytosolic compartment. I-Ad-restricted T cell clones that recognize synthetic peptides corresponding to two distinct antigenic regions of the HA1 subunit, HA1 56-76 and HA1 177-199, are cytotoxic and, dependent on epitope specificity can recognize endogenously processed Ag and lyse class II+ target cells infected with a recombinant vaccinia-X31 HA virus. HA1 56-76 specific T cell clones fail to recognize (target cells infected with) influenza X31 viruses, containing a single residue change, HA1 63 Asp----Asn that introduces an oligosaccharide attachment site: Asp63Cys64Thr65. Recognition is restored, however, by tunicamycin treatment of mutant virus infected target cells. Inasmuch as N-glycosylation of nascent hemagglutinin polypeptides occurs in the lumen of the endoplasmic reticulum, this indicates a route of endogenous processing for hemagglutinin, requiring transport across the endoplasmic reticulum, which has been confirmed by the failure of CD4+ T cells to recognize a recombinant VACC-hemagglutinin virus in which the same single residue change, HA1 63 Asp----Asn has been introduced by site directed mutagenesis.
有证据表明存在一种内源性的抗原加工途径，用于CD4 + T细胞识别流感血凝素，该途径要求新合成的血凝素在内质网腔中进行强制性运输，以便在胞质区室中进行加工。识别HA1亚基两个不同抗原区域（HA1 56 - 76和HA1 177 - 199）对应合成肽段的I - Ad限制性T细胞克隆具有细胞毒性，并且根据表位特异性，能够识别内源性加工的抗原并裂解感染重组痘苗 - X31 HA病毒的II类 + 靶细胞。HA1 56 - 76特异性T细胞克隆无法识别含有单个残基变化（HA1 63 Asp→Asn，引入一个寡糖附着位点：Asp63Cys64Thr65）的流感X31病毒感染的靶细胞。然而，用衣霉素处理突变病毒感染的靶细胞可恢复识别。由于新生血凝素多肽的N - 糖基化发生在内质网腔中，这表明血凝素存在一种内源性加工途径，需要跨内质网运输，这已通过CD4 + T细胞无法识别通过定点诱变引入相同单个残基变化（HA1 63 Asp→Asn）的重组VACC - 血凝素病毒得到证实。
