QA-1B IN PRESENTATION OF ALPHA/BETA AND GAMMA/DELTA LIGANDS TO T CELLS

I类分子qa-1是一种合成的伽马三角洲共聚物。 T细胞。我们现在已经鉴定出一种内源性的九聚体(称为qdm)。 Qa-1b呈递给多肽特异性同种异体反应的α-βT细胞。 有了这个QDM探测器，我们现在处于一个独特的位置来确定 I分子将α-β与伽马-三角洲配体分别呈现给它们各自的 T细胞。此外，我们还将确定该分子在 介绍两种致病微生物李斯特氏菌的表位 单核细胞增多症和小鼠肝炎病毒，转化为CD8+细胞。 为了剖析α-β和伽马-三角洲配体的Qa-1b呈现形式，我们 将使用QDM作为α-βT细胞的配体，并(Glu50Tyr50) (简写为GT)和牛分枝杆菌Hsp65多肽作为伽马-三角洲的配体 T细胞。我们将确定GT或Hsp65是否与Qdm-肽竞争 提供给QDM特异性的α-β细胞毒性T淋巴细胞(CTL)。 相反，我们将确定QDM-肽是否竞争 Qa-1b呈递GT给抗原特异性的γ-Delta杂交瘤的能力。 这些实验将通过抗原结合和竞争来扩大 化验。 单核细胞增多性乳杆菌是一种机会性的病原体，它优先感染 免疫功能受损的个体。李斯特菌溶血素O的一个表位 分子由Qa-1b呈递给CTL。我们将用一种新的多肽 可能的QA-1b结合基序和/或从感染的人中提取肽(S) 细胞，并确定其身份。冠状病毒，是一种常见的 人类常见的感冒。小鼠肝炎病毒是一种常被研究的小鼠 冠状病毒，其HE蛋白含有QDM-肽序列。QA-1b 应该能够将这个表位呈现给CD8+T细胞。我们将决定 小鼠对这种病毒的免疫反应，无论是自然含有还是 缺乏QDM-肽。

The class I molecule, Qa-1, presents a synthetic copolymer to gamma-delta T cells. We have now identified an endogenous nonamer peptide (termed Qdm) that Qa-1b presents to peptide-specific alloreactive alpha-beta T cells. With this Qdm probe we are now in a unique position to determine how class I molecules present alpha-beta vs. gamma-delta ligands to their respective T cells. In addition we will establish what role this molecule plays in presenting epitopes from two pathogenic microorganisms, Listeria monocytogenes and murine hepatitis virus, to CD8+ cells. To dissect Qa-1b presentation of alpha-beta vs. gamma-delta ligands, we will use Qdm as a ligand for alpha-beta T cells, and (Glu50Tyr50) (abbreviated GT) and M. bovis Hsp65 peptides as a ligand for gamma-delta T cells. We will determine whether GT or Hsp65 competes with Qdm-peptide for presentation to Qdm-specific alpha-beta cytotoxic T lymphocytes (CTL). Conversely, we will determine whether the Qdm-peptide competes for the ability of Qa-1b to present GT to antigen specific gamma-delta hybridomas. These experiments will be extended by antigen binding and competition assays. L. monocytogenes is an opportunistic agent which preferentially infects immunocompromised individuals. An epitope from the listeriolysin O molecule is presented to CTL by Qa-1b. We will synthesize peptides with a putative Qa-1b binding motif and/or extract the peptide(s) from infected cells and determine its identity. Coronavirus and is a frequent cause of common colds in man. Murine hepatitis virus is a commonly studied mouse coronavirus whose HE protein contains the Qdm-peptide sequence. Qa-1b should be able to present this epitope to CD8+ T cells. We will determine the immune response to this virus in mice that either naturally contain or lack the Qdm-peptide.