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

I类分子Qa-1是一种合成共聚物， T细胞。我们现在已经确定了一个内源性九聚体肽（称为Qdm） Qa-1b呈递给肽特异性同种异体反应性α-β T细胞。 有了这个Qdm探针，我们现在处于一个独特的位置，以确定类 I分子将α-β与γ-δ配体呈递给它们各自的 T细胞。 此外，我们将确定这种分子在 来自两种病原微生物李斯特菌的呈递表位 单核细胞增多症和鼠肝炎病毒，至CD 8+细胞。 为了剖析α-β与γ-δ配体的Qa-1b呈递，我们 将使用Qdm作为α-β T细胞的配体，并且（Glu 50 Tyr 50） （简称GT）和M.牛Hsp 65肽作为γ-δ配体 T细胞。我们将确定GT或Hsp 65是否与Qdm-肽竞争 用于呈递给Qdm特异性α-β细胞毒性T淋巴细胞（CTL）。 相反地，我们将确定Qdm-肽是否竞争肽。 Qa-1b向抗原特异性γ-δ杂交瘤呈递GT的能力。 这些实验将通过抗原结合和竞争来扩展 测定。 L. 单核细胞增多症是一种机会因子， 免疫力低下的人。一个来自大肠杆菌溶血素O的表位 分子通过Qa-1b呈递给CTL。我们将合成多肽， 假定的Qa-1b结合基序和/或从感染的 细胞并确定其身份。冠状病毒是一种常见的原因， 人类常见的感冒。鼠肝炎病毒是一种常见的研究小鼠 其HE蛋白含有Qdm-肽序列的冠状病毒。Qa-1b 应该能够将该表位呈递给CD 8 + T细胞。我们将确定 小鼠对这种病毒的免疫反应， 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.