The quantity of naturally processed peptides stably bound by HLA-A*0201 is significantly reduced in the absence of tapasin

被引:26
作者
Barber, LD
Howarth, M
Bowness, P
Elliott, T
机构
[1] John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England
[2] John Radcliffe Hosp, Inst Mol Med, Human Immunol Unit, Oxford OX3 9DU, England
来源
TISSUE ANTIGENS | 2001年 / 58卷 / 06期
关键词
endogenous peptides; HLA-A*0201; HLA-B*2705; tapasin;
D O I
10.1034/j.1399-0039.2001.580604.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tapasin plays a critical role in promoting peptide binding by major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum. In its absence, cell surface expression of most allotypes is significantly reduced. Two exceptions are HLA-A*0201 and HLA-B*2705. In this study, the repertoire of peptides bound endogenously by these allotypes in the absence of tapasin was examined and stability of the HLA class I/peptide complexes assessed. Similar quantities of peptides were recovered from B*2705 complexes expressed in the absence and presence of tapasin and the composition of the peptide pools were not radically different. However, the stability of B*2705 molecules expressed at the surface of tapasin. deficient cells was found to be reduced which suggests there are subtle changes to the peptide repertoire. The impact of the absence of tapasin was more dramatic for A*0201. Although equivalent levels of cell surface A*0201 are expressed in the presence and absence of tapasin, very little A*0201 glycoprotein was recovered from tapasin-deficient cells suggesting the complexes readily dissociate. Consistent with reduced stability, A*0201 complexes were found to be rapidly lost from the surface of tapasin-deficient cells. Analysis of the small quantity of endogenously bound peptides recovered from A*0201 expressed in the absence of tapasin revealed a complex mixture typical of A*0201 molecules expressed in normal cells. Therefore these molecules are unable to exploit the alternative supply of TAP-independent A*0201-binding peptides present in the endoplasmic reticulum. Loading of A*0201 with peptides from both TAP-dependent and TAP-independent sources is significantly compromised without tapasin.
引用
收藏
页码:363 / 368
页数:6
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