ROLE OF CLASS IB ANTIGENS AND OPPORTUNISTIC INFECTIONS

描述(改编自申请者的摘要)：非经典 Ib类分子Qa-1是一种合成的伽马/三角洲共聚物 (伽马/增量)T细胞。调查员现在已经确定了一个 Qa-1b呈递给的内源性九聚体(QDM) 多肽特异性同种异体反应性α/β(α/β)T细胞。有了这个 QDM探测器，调查员现在处于一个独特的位置来确定如何 I类分子代表α/βT细胞与γ/β配体 它们各自的T细胞。此外，福尔曼博士将建立 这个分子在呈现两个表位中扮演了什么角色 致病微生物、单核细胞增多性乳杆菌和MHV对CD8+细胞的作用。 为了剖析α/β与伽马/三角洲配体的Qa-1b呈现， 研究人员将使用Qdm作为α/βT的配基 细胞，GluTyr(GT)与牛分枝杆菌热休克蛋白65的共聚物作为 γ/增量T细胞的配基。他将决定GT或Hsp65 与Qdm-肽竞争呈现给Qdm特定的 α/β细胞毒性T淋巴细胞(CTL)。反之， 研究人员将确定QDM-肽是否竞争 Qa-1b呈递GT给抗原特异性γ/Delta T的能力 细胞。这些实验将通过抗原结合和 竞争分析。QA-1b还将受到 位于抗原结合袋内或外的氨基酸 确定这对α/β与伽马/增量的呈现有何影响 配基。 单核细胞增多性乳杆菌是一种机会性因子，它优先于 感染免疫功能受损的人。李斯特菌溶血素的一个表位 O分子由Qa-1b呈递给CTL。调查员将 合成具有假定的Qa-1b结合基序和/或提取物的多肽 从感染细胞中分离出S多肽，并确定其身份。MHV是 一种普遍研究的冠状病毒，是一种常见的 人类患感冒。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CD8+T细胞。这个 研究人员将确定小鼠对这种病毒的免疫反应 天然含有或不含有QDM-肽的。

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.