ANTIGEN PRESENTATION BY CLASS IB MOLECULE, QA-1

Qa-1/HLA-E向NK细胞上的CD/NKG 2受体呈现非常相似的I类前导衍生肽。CD 94/NKG 2受体似乎是MHC限制性的，因为它们识别Ib类分子以及特异性肽。因此，前导衍生肽的呈递对于靶细胞触发NK细胞上的受体的能力至关重要。从D区分子产生鼠肽，我们称之为Qdm，以及从HLA分子产生Qdm样肽，是TAP依赖性的。我们先前已经表明，1）从成熟Dd分子加工Qdm肽不依赖于蛋白酶体活性，2）表位不能通过将Dd引导至胞质溶胶来产生，以及3）Tap功能是将肽从胞质溶胶转运至ER，而不是充当ER中肽装载的辅助分子。有几个问题，我们将解决有关处理QDM。这包括确定E3/19 K前导序列靶向ER的Dd前导序列是否可以在该隔室中加工，改变前导序列N区的变化是否会改变其细胞内运输，蛋白酶在该过程中的作用，以及侧翼残基如何影响加工。据报道，其他前导序列衍生的表位由TAP缺陷型T2细胞中的I类分子呈递。这个问题将通过检查这些表位在其他细胞类型中的呈递来解决。两种病毒，MHV和HCMV，具有编码Qdm或Qdm样表位的基因。我们将确定这些病毒基因以及完整的病毒是否允许Qdm在感染的细胞中表达。如果发生这种情况，我们将检查这些病毒编码的Qdm表位的加工和呈递。

Qa-1/HLA-E present very similar class I leader-derived peptides to CD/NKG2 receptors on NK cells. CD94/NKG2 receptors appear to be MHC restricted in that they recognize both the class Ib molecule as well as specific peptides. Thus, the presentation of the leader derived peptide is critical for the ability of target cells to trigger receptors on NK cells. The generation of the murine peptide from D-region molecules, which we refer to as Qdm, as well as the Qdm-like peptide from HLA molecules, as Tap-dependent. We have previously shown that 1)processing of the Qdm peptide from mature Dd molecules is independent of proteasome activity, 2) the epitope cannot be generated by directing Dd to the cytosol, and 3) Tap functions to transport the peptide from the cytosol to the ER rather than serving as an accessory molecule for peptide loading in the ER. There are several issues that we will address concerning the processing of Qdm. This includes determining whether the Dd leader targeted to the ER by the E3/19K leader can be processed in this compartment, whether altering the change in the N-region of the leader changes its intracellular trafficking, the role of proteases in this process, and how flanking residues affect processing. Other leader derived epitopes have been reported to be presented by class I molecules in Tap-deficient T2 cells. This issue will be addressed by examining the presentation of these epitopes in other cell types. Two viruses, MHV and HCMV, have genes which encode Qdm or Qdm-like epitopes. We will determine whether these viral genes, as well as the intact viruses, allow for Qdm expression in infected cells. If this occurs, we will then examine the processing and presentation of these viral encoded Qdm epitopes.