Differences in peptide presentation between B27 subtypes: the importance of the P1 side chain in maintaining high affinity peptide binding to B*2703.
Differences in peptide presentation between B27 subtypes: the importance of the P1 side chain in maintaining high affinity peptide binding to B*2703.
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DOI：
10.1016/1074-7613(94)90105-8
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发表时间：
1994-05
期刊：
影响因子：
32.4
通讯作者：
R. Colbert;S. Rowland-Jones;A. McMichael;J. Frelinger
中科院分区：
文献类型：
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作者：
R. Colbert;S. Rowland-Jones;A. McMichael;J. Frelinger
对脊椎关节病的敏感性很强。与MHC I类分子HLA-827相关，并且被假设是由致关节炎肽的呈递引起的。827的亚型在结构上有差异，但与疾病相关，应该能够呈递这些肽，而非疾病相关的亚型则不能。我们证明，8 '2703，主要的西非827亚型，可能不容易患病，是不承认的大多数6' 2703。同种反应性CTL，并且不能有效呈递已知的B-2705限制性流感A核蛋白（NP）肽。我们显示低效的呈递是由于NP肽的8 '2703的结合亲和力降低。此外，在NP肽的P1处取代天然存在的Ser的Arg恢复了高亲和力MnD 3和8 '2703的有效呈递。我们的结果表明，8 ′ 2703将仅结合并有效地呈递与8 ′ 2705结合的肽的子集，特别是在P1处具有Arg或Lys的那些肽。携带8 '2703的个体中明显缺乏疾病可能是由于不能结合和呈递推定的致关节炎肽。
Susceptibility to spondyloarthropathles Is strongly as. sociated with the MHC class I molecule HLA-827, and is hypothesized to result from the presentation of arthritogenic peptides. Subtypes of 827 that dlffer structurally but are disease-associated ought to be capable of presenting such peptides, while nondiseaseassociated subtypes would not. We demonstrate that 8’2703, the predominant West African 827 subtype that may not predispose to disease, Is not recognized by most 6’2703. alloreactlve CTL, and does not efflciently present a known B” 2705restricted influenza A nucleoproteln(NP) peptide. We show inefficient presentation is due to a reduced binding affinity of 8’2703 for the NP peptide. Furthermore, substltutlng Arg for the naturally occurring Ser at Pl of the NP peptlde, restores high affinity Mndlng and efficient presentation by 8’2703. Our results suggest that 8’2703 will bind and present efficiently only a subset of the pep tides that bind to 8’2705, in particular those with Arg or Lys at Pl. The apparent lackof disease in Individuals with 8’2703 may be due to an inability to bind and present putative arthritogenic peptides.