Thude H, Hundrieser J, Wonigeit K, Schwinzer R
Klinik für Abdominal- und Transplantationschirurgie Medizinische Hochschule Hannover, Hannover, Germany.
Eur J Immunol. 1995 Jul;25(7):2101-6. doi: 10.1002/eji.1830250745.
CD45 is a receptor-type protein tyrosine phosphatase involved in the regulation of lymphocyte activation. Different CD45 isoforms are generated by alternative splicing of three variable exons (A, B and C). The pattern of CD45 splicing depends upon cell type and state of activation. CD45RA isoforms (containing exon A-encoded sequences) can usually be found on a subset of resting T cells, but not on activated T cells. We have recently described a variant pattern of CD45RA expression which is characterized by continuous expression of CD45RA molecules on activated and memory T cells. Here, we demonstrate that this phenotype is associated with heterozygosity for a point mutation at nucleotide position 77 of exon A, leading to a C-->G transition. This mutation does not change the protein sequence of the CD45RA isoform. We conclude that position 77 is part of a motif necessary for splicing of exon A, which supports the hypothesis that sequences within exons have significant effects on alternative splicing. The mutation of this motif might prevent binding of a transacting splice factor. In the heterozygous state, this mutation is not associated with impaired T cell reactivity. Functional consequences of the homozygous state remain to be elucidated.
CD45是一种参与淋巴细胞激活调节的受体型蛋白酪氨酸磷酸酶。三种可变外显子（A、B和C）的可变剪接产生了不同的CD45异构体。CD45的剪接模式取决于细胞类型和激活状态。CD45RA异构体（包含外显子A编码序列）通常可在一部分静止T细胞上发现，但在活化T细胞上则没有。我们最近描述了一种CD45RA表达的变异模式，其特征是活化T细胞和记忆T细胞上持续表达CD45RA分子。在此，我们证明这种表型与外显子A核苷酸位置77处的一个点突变的杂合性有关，该突变导致C→G转换。此突变不改变CD45RA异构体的蛋白质序列。我们得出结论，位置77是外显子A剪接所需基序的一部分，这支持了外显子内序列对可变剪接有显著影响这一假说。该基序的突变可能会阻止反式作用剪接因子的结合。在杂合状态下，此突变与T细胞反应性受损无关。纯合状态的功能后果仍有待阐明。
