studies of antigen presentation of peptides by MHC class I molecules

1.我们发现HLA-B35分子的组装速度比HLA-B51分子快。可以推测，肽与这些HLA I类分子的结合亲和力的差异导致组装速率的差异。为了研究肽与HLA I类分子的结合，我们使用转染HLA I类基因的RMA-S细胞建立了新的结合试验。分析携带HLA-B35或B51的锚残基的肽与这些HLA I类分子的结合表明，肽与HLA-B51的结合亲和力明显弱于与HLA-B35的结合亲和力。这些结果表明，这些肽在内质网中的组装速率的差异可能是由于肽与这些HLA I类分子结合的差异造成的。2.为了阐明T细胞识别的自身肽，我们尝试分离HLA-B51同种异体反应性CTL识别的同种异体肽。检测到一个HLA-B51同种异体反应性CTL克隆识别的TAP依赖性肽。该方法对抗原提呈和T细胞增殖的研究具有重要意义。3.利用人次要组织相容性抗原（hmH）特异性CTL克隆研究了hmH抗原的多态性和抗原提呈。CTL克隆杀伤大多数表达HLA-B35的靶细胞，而它们不能杀伤表达HLA-B35亚型的细胞。由于特异性hmH肽可以从表达HLA-B35亚型的这些细胞中分离，因此认为hmH抗原在群体中是保守的。

1.We found that assembly rate of HLA-B35 molecules is faster than that of HLA-B51 molecules. One can speculate that the difference of peptide binding affinity to these HLA class I molecules result in that of assembly rate. To investigate peptide binding to HLA class I molecules, we established novel binding assay using RMA-S cells trasnfected with HLA class I genes. Analysis of binding of peptides carrying anchor residues of HLA-B35 or B51 to these HLA class I molecules indicate that the peptide binding affinity to HLA-B51 is significantly weaker than that to HLA-B35. These findings imply that the difference of assembly rate may result from that of peptide binding to these HLA class I molecules in endoplasmic reticurum.2.In order to clarify self-peptides recognized by T cells, we attempted to isolate allopeptides recognized by HLA-B51 alloreactive CTL.In HPLC fraction of peptides isolated from purified HLA-B51 molecules, a TAP dependent peptide recognized by one HLA-B51 alloreactive CTL clone was detected. This approach is very useful for studies of antigen presentation and T cell recognition.3.Polymorphism and antigen presentation of human minor histocompatibility (hmH) antigens were studied using hmH specific CTL clones. The CTL clones killed most target cells expressing HLA-B35, while they failed to kill the cells expressing HLA-B35 subtypes. Since the specific hmH peptides could be isolated form these cells expressing HLA-B35 subytypes, hmH antigens are thought to be conserved among populations.