CLASS IB ANTIGENS AND OPPORTUNISTIC INFECTIONS

描述（改编自申请人的摘要）：非经典 Ib类分子Qa-1是一种合成的共聚物， （γ/δ）T细胞。调查人员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（α/β）T细胞。与此 QDM探测器，调查人员现在处于一个独特的位置，以确定如何 I类分子将α/β T细胞与γ/δ配体呈递给 各自的T细胞。此外，福尔曼博士将建立 这个分子在呈递来自两个 病原微生物L.单核细胞增多症和MHV至CD 8+细胞。 为了剖析α/β与γ/δ配体的Qa-1b呈递， 研究者将使用Qdm作为α/β T配体 细胞，以及共聚物GluTyr（GT）和M.牛Hsp 65肽作为一种 γ/δ T细胞的配体。他将决定GT还是HSP 65 与Qdm-肽竞争呈递给 量子点特异性 α/β细胞毒性T淋巴细胞（CTL）。 反之， 研究者将确定Qdm-肽是否竞争 Qa-1b将GT呈递给抗原特异性γ/δ T的能力 细胞这些实验将通过抗原结合来扩展， 竞争测定。Qa-1b也将进行以下诱变： 位于抗原结合口袋内或外的氨基酸 以确定这如何影响α/β与γ/δ的呈现 配体。 L. 单核细胞增多症是一种机会因子， 感染免疫力低下的个体。来自李斯特菌溶血素的表位 O分子由Qa-1b提呈给CTL。研究者将 合成具有推定Qa-1b结合基序的肽和/或提取物 从感染的细胞中分离肽并确定其身份。 MHV是 一种通常被研究的冠状病毒， 这种病毒含有Qdm-肽序列，因此 Qa-1b应该能够将该表位呈递给CD 8 + T细胞。的 研究人员将确定小鼠对该病毒的免疫反应 天然含有或缺乏Qdm-肽。

DESCRIPTION (Adapted from applicant's abstract): The non-classical class Ib molecule, Qa-1, presents a synthetic copolymer to gamma/delta (gamma/delta) T cells. The investigator has now identified an endogenous nonamer peptide (termed Qdm) that Qa-1b presents to peptide-specific alloreactive alpha/beta (alpha/beta) T cells. With this Qdm probe, the investigator is now in a unique position to determine how class I molecules present alpha/beta T cells vs. gamma/delta ligands to their respective T cells. In addition, Dr. Forman will establish what role this molecule plays in presenting epitopes from two pathogenic microorganisms, L. monocytogenes and MHV to CD8+ cells. To dissect Qa-1b presentation of alpha/beta vs. gamma/delta ligands, the investigator will use Qdm as a ligand for alpha/beta T cells, and the copolymer GluTyr (GT) and M. bovis Hsp65 peptides as a ligand for gamma/delta T cells. He will determine whether GT or Hsp65 competes with Qdm-peptide for presentation to Qdm-specific alpha/beta cytotoxic T lymphocytes (CTL). Conversely, the investigator will determine whether the Qdm-peptide competes for the ability of Qa-1b to present GT to antigen specific gamma/delta T cells. These experiments will be extended by antigen binding and competition assays. Qa-1b will also be subjected to mutagenesis of amino acids located within or out of the antigen binding pocket to determine how this affects presentation of alpha/beta vs gamma/delta ligands. 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. The investigator will synthesize peptides with a putative Qa-1b binding motif and/or extract the peptide(s) from infected cells and determine its identity. MHV is a commonly studied coronavirus and is a frequent cause of common colds in man. This virus contains the Qdm-peptide sequence and thus Qa-1b should be able to present this epitope to CD8+ T cells. The investigator will determine the immune response to this virus in mice that either naturally contain or lack the Qdm-peptide.