Schirmbeck R, Böhm W, Melber K, Reimann J
Institute for Medical Microbiology, University of Ulm, Germany.
J Immunol. 1995 Nov 15;155(10):4676-84.
Many cell types efficiently present an epitope of the hepatitis B surface Ag (HBsAg) to murine class I-restricted CTL following an in vitro pulse with native 22-nm HBsAg particles. Processing of exogenous HBsAg particles required its cytochalasin B-insensitive uptake and acid proteolysis in an endocytic compartment, was insensitive to brefeldin A and cycloheximide, and did not involve regurgitation of antigenic peptides. In contrast, after an in vitro pulse of cells with exogenous, heat-denatured 1-micron HBsAg aggregates, only macrophages (but not other cell types tested) presented the Ld-restricted HBsAg epitope efficiently to CTL. Processing of exogenous HBsAg aggregates required its cytochalasin B-sensitive uptake, was insensitive to brefeldin A, and involved regurgitation of antigenic peptides. Processing of the two different, exogenous HBsAg preparations for class I-restricted epitope presentation thus involved alternative pathways: an "endocytic pathway" for native 22-nm particles, and a "phagocytic pathway" for denatured 1-microns aggregates. Both HBsAg preparations displayed different immunogenicity for class I-restricted CTL in vivo when delivered without adjuvants: native HBsAg particles were of high immunogenicity, and denatured HBsAg aggregates were of low immunogenicity. Class I-restricted CTL are thus primed in vivo after "endocytic processing" of native HBsAg particles as well as "phagocytic processing" of denatured HBsAg aggregates.
许多细胞类型在体外与天然22纳米乙肝表面抗原（HBsAg）颗粒脉冲孵育后，能有效地将HBsAg的一个表位呈递给小鼠I类限制性细胞毒性T淋巴细胞（CTL）。外源性HBsAg颗粒的加工需要其在细胞松弛素B不敏感的情况下摄取，并在内吞区室中进行酸性蛋白水解，对布雷菲德菌素A和放线菌酮不敏感，且不涉及抗原肽的反流。相比之下，用外源性热变性的1微米HBsAg聚集体对细胞进行体外脉冲处理后，只有巨噬细胞（而非其他测试的细胞类型）能有效地将Ld限制性HBsAg表位呈递给CTL。外源性HBsAg聚集体的加工需要其在细胞松弛素B敏感的情况下摄取，对布雷菲德菌素A不敏感，且涉及抗原肽的反流。因此，这两种不同的外源性HBsAg制剂用于I类限制性表位呈递的加工涉及不同途径：天然22纳米颗粒的“内吞途径”和变性1微米聚集体的“吞噬途径”。当无佐剂递送时，两种HBsAg制剂在体内对I类限制性CTL显示出不同的免疫原性：天然HBsAg颗粒具有高免疫原性，而变性HBsAg聚集体具有低免疫原性。因此，I类限制性CTL在体内经天然HBsAg颗粒的“内吞加工”以及变性HBsAg聚集体的“吞噬加工”后被激活。
