CLASS-II-RESTRICTED PRESENTATION OF AN ENDOGENOUSLY DERIVED IMMUNODOMINANT T-CELL DETERMINANT OF HEN EGG LYSOZYME
CLASS-II-RESTRICTED PRESENTATION OF AN ENDOGENOUSLY DERIVED IMMUNODOMINANT T-CELL DETERMINANT OF HEN EGG LYSOZYME
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DOI：
10.1073/pnas.88.8.3290
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发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
MCCLUSKEY, J
中科院分区：
文献类型：
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作者：
BROOKS, A;HARTLEY, S;MCCLUSKEY, J
体外模型用于研究主要组织相容性复合物 II 类分子加工和呈递不同结构形式的内源抗原的潜力。 为此目的，在用编码 HEL 分子的基因转染的 II 类阳性 B 淋巴瘤细胞 (M12.C3) 中研究了鸡蛋溶菌酶 [HEL-(46-61)] 的免疫显性表位的 II 类限制性呈递，这些分子 (i) 以高 (hi) 或低 (lo) 量分泌作为可溶性抗原 [(s)HEL(hi/lo)]，(ii) 定位于内质内网织 (ER)/救助室 ((ER)HEL)，或 (iii) 作为整合膜蛋白 ((m)HEL) 锚定在细胞表面。 相应的 (s)HEL、(ER)HEL 和 (m)HEL 基因产物的表达与预测一致，只是 HEL 决定簇在培养物上清液中以及 (m)HEL 转染细胞的细胞膜上积累。 内源性表达所有三种形式的 HEL 抗原的 II 类阳性细胞组成型呈递免疫显性的 HEL-(46-61) 决定簇，并以不同的效率 ((m)HEL、(S)HEL > (ER)HEL) 向 II 类限制性 T 杂交瘤呈递。 第二个T杂交瘤识别组成型呈递在(s)HEL(hi)和(m)HEL转染子上但不呈递在(s)HEL(lo)或(ER)HEL转染子上的内源HEL-(46-61)决定簇。 因此，(ER)HEL和(S)HEL(lo)转染子中HEL-(46-61)/I-A(k)复合物的形成受到限制。 不同抗原呈递细胞的混合实验表明，HEL-(46-61)决定簇源自内源性抗原，而不是通过重新摄取脱落或分泌的HEL决定簇。 我们得出的结论是，MHC II 类分子可以呈递一些源自内源性蛋白质的抗原决定簇，这些内源性蛋白质被隔离在 ER/抢救室中，并以分泌或膜抗原的形式向远端转运。
An in vitro model was used to investigate the potential for different structural forms of endogenous antigen to be processed and presented by major histocompatibility complex class II molecules. For this purpose the class II-restricted presentation of an immunodominant epitope of hen egg lysozyme [HEL-(46-61)] was studied in class II-positive B-lymphoma cells (M12.C3) transfected with genes encoding HEL molecules either (i) secreted in high (hi) or low (lo) amounts as soluble antigen [(s)HEL(hi/lo)], (ii) localized within the endoplasmic reticulum (ER)/salvage compartment ((ER)HEL), or (iii) anchored on the cell surface as an integral membrane protein ((m)HEL). The corresponding (s)HEL, (ER)HEL, and (m)HEL gene products were expressed as predicted except that HEL determinants accumulated in the culture supernatant as well as on the cell membrane of (m)HEL-transfected cells. Class II-positive cells endogenously expressing all three forms of HEL antigen constitutively presented the immunodominant HEL-(46-61) determinant with differential efficiency ((m)HEL, (S)HEL > (ER)HEL) to a class II-restricted T hybridoma. A second T hybridoma recognized endogenous HEL-(46-61) determinants constitutively presented on (s)HEL(hi) and (m)HEL transfectants but not on (s)HEL(lo) or (ER)HEL transfectants. The formation of HEL-(46-61)/I-A(k) complexes in the (ER)HEL and (S)HEL(lo) transfectants was therefore limiting. Mixing experiments with different antigen-presenting cells indicated that the HEL-(46-61) determinant was derived from endogenous antigen rather than by reuptake of shed or secreted HEL determinants. We conclude that MHC class II molecules can present some antigenic determinants derived from endogenous proteins that are sequestered in the ER/salvage compartment as well as distally transported in the form of secretory or membrane antigens.