DISTINCT H-2-LINKED IR-GENES CONTROL BOTH ANTIBODY AND T-CELL RESPONSES TO DIFFERENT DETERMINANTS ON THE SAME ANTIGEN, MYOGLOBIN

DISTINCT H-2-LINKED IR-GENES CONTROL BOTH ANTIBODY AND T-CELL RESPONSES TO DIFFERENT DETERMINANTS ON THE SAME ANTIGEN, MYOGLOBIN
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DOI:
10.1073/pnas.76.8.4046
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发表时间:
1979-01-01
影响因子:
11.1
通讯作者:
KILLION, DJ
KILLION, DJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BERZOFSKY, JA;RICHMAN, LK;KILLION, DJ

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小鼠抗体和T [胸腺衍生]淋巴细胞对抹香鲸肌红蛋白(Mb)的增殖反应受2种不同的H-2连锁免疫反应(Ir)基因(Ir-Mb-1,定位于I-A亚区,Ir-Mb-2,定位于I-C)的控制。具有两种基因的H-2d小鼠(B10.D2和DBA/2)对Mb及其片段的抗体分泌和T细胞增殖均具有高应答,而H-2b(B10)和H-2k(B10.BR)小鼠则具有低应答。仅具有Ir-Mb-2的菌株[B10.A和B10.A(5 R)]是Mb的中间应答者,当用Mb免疫时,产生针对NH 2-末端片段(1-55)的抗体并响应于其增殖,但不产生针对COOH-末端片段(132-153)的抗体并响应于其增殖。相比之下,仅携带Ir-Mb-1基因的小鼠(D2.GD和B10.GD)对两种片段产生抗体并增殖。然而,它们对片段(1-55)的增殖通常低于它们的同源高应答者(分别为DBA/2和B10.D2),这可能是因为它们仅对该NH 2末端片段上的一些决定子应答。不同的Ir基因,映射在不同的I-亚区的H-2,控制反应不同的抗原决定簇上相同的蛋白质分子。此外,控制T淋巴细胞对给定决定子的反应的基因也控制对相同决定子(或密切相关的决定子)特异性的抗体的产生。
The murine antibody and T [thymus-derived] lymphocyte proliferative responses to sperm whale myoglobin (Mb) were under control of 2 distinct H-2-linked immune response (Ir) genes (Ir-Mb-1, mapping in the I-A subregion, and Ir-Mb-2, mapping in I-C). H-2d mice (B10.D2 and DBA/2), with both genes, were high responders to Mb and its fragments for both antibody secretion and T cell proliferation, while H-2b (B10) and H-2k (B10.BR) mice were low responders. Strains with only Ir-Mb-2 [B10.A and B10.A(5R)], which were intermediate responders to Mb, made antibodies to and proliferated in response to the NH2-terminal fragment (1-55) but not the COOH-terminal fragment (132-153) when immunized with Mb. In contrast, mice carrying only the Ir-Mb-1 gene (D2.GD and B10.GD) made antibodies to and proliferated in response to both fragments. However, their proliferation to fragment (1-55) was often lower than that of their congenic high responders (DBA/2 and B10.D2, respectively), possibly because they respond to only some of the determinants on this NH2-terminal fragment. Distinct Ir genes, mapping in separate I-subregions of H-2, control responses to different antigenic determinants on the same protein molecule. Moreover, the gene that controls the T lymphocyte responses to a given determinant also controls production of antibodies specific for that same determinant (or a closely associated one).